ICU- and ventilator-free days with isoflurane or propofol as a primary sedative - A post- hoc analysis of a randomized controlled trial.

PURPOSE: To compare ICU-free (ICU-FD) and ventilator-free days (VFD) in the 30 days after randomization in patients that received isoflurane or propofol without receiving the other sedative. MATERIALS AND METHODS: A recent randomized controlled trial (RCT) compared inhaled isoflurane via the Sedaconda® anaesthetic conserving device (ACD) with intravenous propofol for up to 54 h (Meiser et al. 2021). After end of study treatment, continued sedation was locally determined. Patients were eligible for this post-hoc analysis only if they had available 30-day follow-up data and never converted to the other drug in the 30 days from randomization. Data on ventilator use, ICU stay, concomitant sedative use, renal replacement therapy (RRT) and mortality were collected. RESULTS: Sixty-nine of 150 patients randomized to isoflurane and 109 of 151 patients randomized to propofol were eligible. After adjusting for potential confounders, the isoflurane group had more ICU-FD than the propofol group (17.3 vs 13.8 days, p = 0.028). VFD for the isoflurane and propofol groups were 19.8 and 18.5 respectively (p = 0.454). Other sedatives were used more frequently (p < 0.0001) and RRT started in a greater proportion of patients in the propofol group (p = 0.011). CONCLUSIONS: Isoflurane via the ACD was not associated with more VFD but with more ICU-FD and less concomitant sedative use.

Healthcare workers' experiences of patient safety in the intensive care unit during the COVID-19 pandemic: A multicentre qualitative study.

AIM: To describe healthcare workers' experiences of preconditions and patient safety risks in intensive care units during the COVID-19 pandemic. BACKGROUND: Healthcare workers' ability to adapt to changing conditions is crucial to promote patient safety. During the COVID-19 pandemic, healthcare workers' capacity to maintain safe care was challenged and a more in-depth understanding on frontline experiences of patient safety is needed. DESIGN: A qualitative descriptive design. METHODS: Individual interviews were conducted with 29 healthcare workers (nurses, physicians, nurse assistants and physiotherapists) from three Swedish hospitals directly involved in intensive care of COVID-19 patients. Data were analysed with inductive content analysis. Reporting followed the COREQ checklist. RESULTS: Three categories were identified. Hazardous changes in working conditions describes patient safety challenges associated with the extreme workload with high stress level. Imperative adaptations induced by changed preconditions for patient safety which include descriptions of safety risks following adaptations related to temporary intensive care facilities, handling shortage of medical equipment and deviations from routines. Safety risks triggered by reorganisation of care describe how the diluted skill-mix and team disruptions exposed patients to safety risks, and that safety performance mostly relied on individual healthcare worker's responsibility. CONCLUSIONS: The study suggests that healthcare workers experienced an increase in patient safety risks during the COVID-19 pandemic mainly because the extremely high workload, imperative adaptations, and reorganisation of care regarding skill-mix and teamwork. Patient safety performance relied on the individuals' adaptability and responsibility rather than on system-based safety. RELEVANCE TO CLINICAL PRACTICE: This study provides insights on how healthcare workers' experiences can be used as a source of information for recognition of patient safety risks. To improve detection of safety risks during future crises, guidelines on how to approach safety from a system perspective must include healthcare workers' perceptions on safety risks. PATIENT AND PUBLIC CONTRIBUTION: None in the conceptualisation or design of the study.

Ventilatory Effects of Isoflurane Sedation via the Sedaconda ACD-S versus ACD-L: A Substudy of a Randomized Trial.

Devices used to deliver inhaled sedation increase dead space ventilation. We therefore compared ventilatory effects among isoflurane sedation via the Sedaconda ACD-S (internal volume: 50 mL), isoflurane sedation via the Sedaconda ACD-L (100 mL), and propofol sedation with standard mechanical ventilation with heat and moisture exchangers (HME). This is a substudy of a randomized trial that compared inhaled isoflurane sedation via the ACD-S or ACD-L to intravenous propofol sedation in 301 intensive care patients. Data from the first 24 h after study inclusion were analyzed using linear mixed models. Primary outcome was minute ventilation. Secondary outcomes were tidal volume, respiratory rate, arterial carbon dioxide pressure, and isoflurane consumption. In total, 151 patients were randomized to propofol and 150 to isoflurane sedation; 64 patients received isoflurane via the ACD-S and 86 patients via the ACD-L. While use of the ACD-L was associated with higher minute ventilation (average difference (95% confidence interval): 1.3 (0.7, 1.8) L/min, p < 0.001), higher tidal volumes (44 (16, 72) mL, p = 0.002), higher respiratory rates (1.2 (0.1, 2.2) breaths/min, p = 0.025), and higher arterial carbon dioxide pressures (3.4 (1.2, 5.6) mmHg, p = 0.002), use of the ACD-S did not significantly affect ventilation compared to standard mechanical ventilation and sedation. Isoflurane consumption was slightly less with the ACD-L compared to the ACD-S (-0.7 (-1.3, 0.1) mL/h, p = 0.022). The Sedaconda ACD-S compared to the ACD-L is associated with reduced minute ventilation and does not significantly affect ventilation compared to a standard mechanical ventilation and sedation setting. The smaller ACD-S is therefore the device of choice to minimize impact on ventilation, especially in patients with a limited ability to compensate (e.g., COPD patients). Volatile anesthetic consumption is slightly higher with the ACD-S compared to the ACD-L.

Isoflurane vs. propofol for sedation in invasively ventilated patients with acute hypoxemic respiratory failure: an a priori hypothesis substudy of a randomized controlled trial.

BACKGROUND: Acute hypoxemic respiratory failure (AHRF) is a leading concern in critically ill patients. Experimental and clinical data suggest that early sedation with volatile anesthestics may improve arterial oxygenation and reduce the plasma and alveolar levels of markers of alveolar epithelial injury and of proinflammatory cytokines. METHODS: An a priori hypothesis substudy of a multicenter randomized controlled trial (The Sedaconda trial, EUDRA CT Number 2016-004551-67). In the Sedaconda trial, 301 patients on invasive mechanical ventilation were randomized to 48 h of sedation with isoflurane or propofol in a 1:1 ratio. For the present substudy, patients with a ratio of arterial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2), PaO2/FiO2, of ≤ 300 mmHg at baseline were included (n = 162). The primary endpoint was the change in PaO2/FiO2 between baseline and the end of study sedation. A subgroup analysis in patients with PaO2/FiO2 ≤ 200 mmHg was performed (n = 82). RESULTS: Between baseline and the end of study sedation (48 h), oxygenation improved to a similar extent in the isoflurane vs. the propofol group (isoflurane: 199 ± 58 to 219 ± 76 mmHg (n = 70), propofol: 202 ± 62 to 236 ± 77 mmHg (n = 89); p = 0.185). On day seven after randomization, PaO2/FiO2 was 210 ± 79 mmHg in the isoflurane group (n = 41) and 185 ± 87 mmHg in the propofol group (n = 44; p = 0.411). In the subgroup of patients with PaO2/FiO2 ≤ 200 mmHg, PaO2/FiO2 increase between baseline and end of study sedation was 152 ± 33 to 186 ± 54 mmHg for isoflurane (n = 37), and 150 ± 38 to 214 ± 85 mmHg for propofol (n = 45; p = 0.029). On day seven, PaO2/FiO2 was 198 ± 69 mmHg in patients randomized to isoflurane (n = 20) and 174 ± 106 mmHg in patients randomized to propofol (n = 20; p = 0.933). Both for the whole study population and for the subgroup with PaO2/FiO2 ≤ 200 mmHg, no significant between-group differences were observed for PaCO2, pH and tidal volume as well as 30-day mortality and ventilator-free days alive. CONCLUSIONS: In patients with AHRF, inhaled sedation with isoflurane for a duration of up to 48 h did not lead to improved oxygenation in comparison to intravenous sedation with propofol. Trial registration The main study was registered in the European Medicines Agency's EU Clinical Trial register (EudraCT), 2016-004551-67, before including the first patient. The present substudy was registered at German Clinical Trials Register (DRKS, ID: DRKS00018959) on January 7th, 2020, before opening the main study data base and obtaining access to study results.

Caregiver burden and emotional wellbeing in informal caregivers to ICU survivors-A prospective cohort study.

BACKGROUND: Informal caregivers to intensive care unit (ICU) survivors may develop post-intensive care syndrome family (PICS-F), including depression, anxiety and post-traumatic stress (PTS). Our primary aim was to investigate associations between caregiver burden in informal caregivers cohabiting with ICU survivors and patients' physical and psychological outcomes. METHODS: A prospective, multicentre cohort study in four ICUs in Sweden. Adults cohabiting with ICU patients included in a previous study were eligible for inclusion. Three months post-ICU, informal caregivers received questionnaires assessing caregiver burden, health-related quality of life (HRQL) and symptoms of depression, anxiety and PTS. In parallel, patients reported their three-month physical and psychological status via validated questionnaires. The primary outcome of this study was to compare caregiver burden in informal caregivers to patients with and without adverse physical and psychological outcomes 3 months post-ICU. Secondary outcomes were correlations between caregiver burden and informal caregivers' mental HRQL. RESULTS: Among 62 included informal caregivers, 55 (89%) responded to the follow-up questionnaires. Caregiver burden was higher among informal caregivers to patients with an adverse outcome, compared to informal caregivers to patients without an adverse outcome, caregiver burden scale score mean (±standard deviation) 52 (11) and 41 (13) respectively (p = 0.003). There was strong negative correlation between caregiver burden and informal caregivers' mental HRQL (rs -0.74, p < 0.001). CONCLUSION: Informal caregivers to ICU survivors with adverse physical or psychological outcome experience a higher caregiver burden. A higher caregiver burden correlates with worse caregiver mental HRQL. ICU follow-up programs should consider screening and follow-up of informal caregivers for mental health problems.

Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial.

BACKGROUND: Previous studies indicate that isoflurane could be useful for the sedation of patients in the intensive care unit (ICU), but prospective studies evaluating isoflurane's efficacy have been small. The aim of this study was to test whether the sedation with isoflurane was non-inferior to sedation with propofol. METHODS: This phase 3, randomised, controlled, open-label non-inferiority trial evaluated the efficacy and safety of up to 54 h of isoflurane compared with propofol in adults (aged ≥18 years) who were invasively ventilated in ICUs in Germany (21 sites) and Slovenia (three sites). Patients were randomly assigned (1:1) to isoflurane inhalation via the Sedaconda anaesthetic conserving device (ACD; Sedana Medical AB, Danderyd, Sweden; ACD-L [dead space 100 mL] or ACD-S [dead space 50 mL]) or intravenous propofol infusion (20 mg/mL) for 48 h (range 42-54) using permuted block randomisation with a centralised electronic randomisation system. The primary endpoint was percentage of time in Richmond Agitation-Sedation Scale (RASS) range -1 to -4, assessed in eligible participants with at least 12 h sedation (the per-protocol population), five or more RASS measurements, and no major protocol violations, with a non-inferiority margin of 15%. Key secondary endpoints were opioid requirements, spontaneous breathing, time to wake-up and extubation, and adverse events. Safety was assessed in all patients who received at least one dose. The trial is complete and registered with EudraCT, 2016-004551-67. FINDINGS: Between July 2, 2017, and Jan 12, 2020, 338 patients were enrolled and 301 (89%) were randomly assigned to isoflurane (n=150) or propofol (n=151). 146 patients (97%) in each group completed the 24-h follow-up. 146 (97%) patients in the isoflurane group and 148 (98%) of patients in the propofol group were included in the per-protocol analysis of the primary endpoint. Least-squares mean percentage of time in RASS target range was 90·7% (95% CI 86·8-94·6) for isoflurane and 91·1% (87·2-95·1) for propofol. With isoflurane sedation, opioid dose intensity was 29% lower than with propofol for the overall sedation period (0·22 [0·12-0·34] vs 0·32 [0·21-0·42] mg/kg per h morphine equivalent dose, p=0·0036) and spontaneous breathing was more frequent on day 1 (odds ratio [OR] 1·72 [1·12-2·64], generalised mixed linear model p=0·013, with estimated rates of 50% of observations with isoflurane vs 37% with propofol). Extubation times were short and median wake-up was significantly faster after isoflurane on day 2 (20 min [IQR 10-30] vs 30 min [11-120]; Cox regression p=0·0011). The most common adverse events by treatment group (isoflurane vs propofol) were: hypertension (ten [7%] of 150 vs two [1%] of 151), delirium (eight [5%] vs seven [5%]), oliguria (seven [5%] vs six [4%]), and atrial fibrillation (five [3%] vs four [3%]). INTERPRETATION: These results support the use of isoflurane in invasively ventilated patients who have a clinical need for sedation. FUNDING: Sedana Medical AB.

Plasma HMGB1 levels and physical performance in ICU survivors.

PURPOSE: Physical impairment after critical illness is recognized as a part of the post-intensive care syndrome (PICS). About one third of intensive care unit (ICU) survivors suffer from long-term physical disability, yet the underlying pathophysiological mechanisms remain poorly understood. The pro-inflammatory alarmin, high mobility group box 1 (HMGB1), promotes muscle dysfunction in experimental models, and HMGB1 stays elevated in some patients after ICU discharge. Accordingly, we investigated the relationship between HMGB1 plasma levels and physical performance in ICU survivors. METHODS: Prospective cohort study of 100 ICU survivors from the general ICU at the Karolinska University Hospital, Sweden. Patients returned for follow up at 3 (58 patients) and 6 months (51 patients) after ICU discharge. Blood samples were collected, and a 6-minute walk test (6-MWT), a handgrip-strength test (HST), and a timed-stands test (TST) were performed. RESULTS: Compared to reference values of the different physical tests, 16% of patients underperformed at all tests at 3 months and 12% at 6 months. All test results, except hand-grip strength left, improved significantly over the follow-up period (P < .05). There was no significant association between plasma HMGB1 levels at 3 and 6 months and scores on the three tests (6-MWT, TST, and HST) (P = .50-0.69). CONCLUSION: In this follow-up study of ICU survivors, we found no significant association between plasma HMGB1 levels and physical performance. Additional follow-up studies of HMGB1 plasma levels and muscle function in ICU survivors are still warranted. EDITORIAL COMMENT: HMGB-1, a marker of cell damage and activation, is known to increase in ICU patients. In study participants at 3- to 6-month post-ICU stay, HMGB-1 levels were still elevated, although no association to the primary outcome, physical performance, was found. Mechanisms for failure to recover physical performance post-ICU remain unclear, and investigations into cause of post-intensive care syndrome need to continue. TRIAL REGISTRATIONS: ClinicalTrials.gov identifier NCT02914756.

ICU discharge screening for prediction of new-onset physical disability-A multinational cohort study.

BACKGROUND: Methods to identify patients at risk for incomplete physical recovery after intensive care unit (ICU) stay are lacking. Our aim was to develop a method for prediction of new-onset physical disability at ICU discharge. METHODS: Multinational prospective cohort study in 10 general ICUs in Sweden, Denmark, and the Netherlands. Adult patients with an ICU stay ≥12 hours were eligible for inclusion. Sixteen candidate predictors were analyzed with logistic regression for associations with the primary outcome; new-onset physical disability 3 months post-ICU, defined as a ≥10 score reduction in the Barthel Index (BI) compared to baseline. RESULTS: Of the 572 included patients, follow-up data are available on 78% of patients alive at follow-up. The incidence of new-onset physical disability was 19%. Univariable and multivariable modeling rendered one sole predictor for the outcome: physical status at ICU discharge, assessed with the five first items of the Chelsea critical care physical assessment tool (CPAx) (odds ratio 0.87, 95% confidence interval (CI) 0.81-0.93), a higher score indicating a lower risk, with an area under the receiver operating characteristics curve of 0.68 (95% CI 0.61-0.76). Negative predictive value for a low-risk group (CPAx score >18) was 0.88, and positive predictive value for a high-risk group (CPAx score ≤18) was 0.32. CONCLUSION: The ICU discharge assessment described in this study had a moderate AUC but may be useful to rule out patients unlikely to need physical interventions post-ICU. For high-risk patients, research to determine post-ICU risk factors for an incomplete rehabilitation is mandated.

Lack of clinically relevant correlation between subjective and objective cognitive function in ICU survivors: a prospective 12-month follow-up study.

BACKGROUND: Cognitive impairment and psychological distress are common in intensive care unit (ICU) survivors. Early identification of affected individuals is important, so intervention and treatment can be utilized at an early stage. Cognitive Failures Questionnaire (CFQ) is commonly used to screen for subjective cognitive function, but it is unclear whether CFQ scores correlate to objective cognitive function in this population. METHODS: Between 2014 and 2018, 100 ICU survivors aged 18-70 years from the general ICU at the Karolinska University Hospital, Solna, were included in the study. Out of these, 58 patients completed follow-up at 3 months after ICU discharge, 51 at 6 months, and 45 at 12 months. Follow-up included objective cognitive function testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and subjective cognitive function testing with the self-rating Cognitive Failures Questionnaire (CFQ), as well as psychological self-rating with the Post-Traumatic Stress Symptoms Scale-10 (PTSS-10) and Hospital Anxiety and Depression Scale (HADS). RESULTS: The prevalence of cognitive impairment as measured by four selected CANTAB tests was 34% at 3 months after discharge, 18% at 6 months, and 16% at 12 months. There was a lack of significant correlation between CANTAB scores and CFQ scores at 3 months (r = - 0.134-0.207, p > 0.05), at 6 months (r = - 0.106-0.257, p > 0.05), and at 12 months after discharge (r = - 0.070-0.109, p > 0.05). Correlations between CFQ and PTSS-10 scores and HADS scores, respectively, were significant over the follow-up period (r = 0.372-0.710, p ≤ 0.001-0.023). In contrast, CANTAB test scores showed a weak correlation with PTSS-10 and HADS scores, respectively, at 3 months only (r = - 0.319-0.348, p = 0.008-0.015). CONCLUSION: We found no clinically relevant correlation between subjective and objective cognitive function in this cohort of ICU survivors, while subjective cognitive function correlated significantly with psychological symptoms throughout the follow-up period. Treatment and evaluation of ICU survivors' recovery need to consider both subjective and objective aspects of cognitive impairment, and subjective reports must be interpreted with caution as an indicator of objective cognitive function.

Measuring pain-Physiological and self-rated measurements in relation to pain stimulation and anxiety.

INTRODUCTION: The aim of the present study was to investigate how emotions influence pain, measured by one subjective self-rated measure, the numeric rating scale (NRS), and one objective physiological measure, the number of skin conductance responses (NSCR). METHOD: Eighteen volunteers were exposed to conditions with pictorial emotional stimuli (neutral, positive, negative), authentic ICU-sound (noise, no-noise) and electrical stimulation (pain, no-pain) individually titrated to induce moderate pain. When using all combinations of picture inducing emotions, sound, and pain, each of these conditions (12 conditions lasting for 60 seconds each) were followed by pain ratings. Ratings of arousal (low to high) and valence (pleasant to unpleasant) were used as indicators of affective state for each condition. Mean NSCR was also measured throughout the experiment for each condition. RESULTS: Even though NRS and NSCR increased during painful stimuli, they did not correlate during the trial. However, NSCR was positively correlated with the strength of the electrical stimulation, r = 0.48, P = 0.046, whereas NRS showed positive correlations with the anxiety level, assessed by affective ratings (arousal, r = 0.61, P < 0.001, and valence, r = 0.37, P < 0.001). CONCLUSIONS: The NRS was strongly influenced by affective state, with higher pain ratings during more anxiety-like states, whereas NSCR correlated to the strength of electrical pain stimulation. That reported pain is moderated by anxiety, puts forward a discussion whether reduction of the anxiety level should be considered during analgesia treatment.

Standardized Unloading of Respiratory Muscles during Neurally Adjusted Ventilatory Assist: A Randomized Crossover Pilot Study.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Currently, there is no standardized method to set the support level in neurally adjusted ventilatory assist (NAVA). The primary aim was to explore the feasibility of titrating NAVA to specific diaphragm unloading targets, based on the neuroventilatory efficiency (NVE) index. The secondary outcome was to investigate the effect of reduced diaphragm unloading on distribution of lung ventilation. METHODS: This is a randomized crossover study between pressure support and NAVA at different diaphragm unloading at a single neurointensive care unit. Ten adult patients who had started weaning from mechanical ventilation completed the study. Two unloading targets were used: 40 and 60%. The NVE index was used to guide the titration of the assist in NAVA. Electrical impedance tomography data, blood-gas samples, and ventilatory parameters were collected. RESULTS: The median unloading was 43% (interquartile range 32, 60) for 40% unloading target and 60% (interquartile range 47, 69) for 60% unloading target. NAVA with 40% unloading led to more dorsal ventilation (center of ventilation at 55% [51, 56]) compared with pressure support (52% [49, 56]; P = 0.019). No differences were found in oxygenation, CO2, and respiratory parameters. The electrical activity of the diaphragm was higher during NAVA with 40% unloading than in pressure support. CONCLUSIONS: In this pilot study, NAVA could be titrated to different diaphragm unloading levels based on the NVE index. Less unloading was associated with greater diaphragm activity and improved ventilation of the dependent lung regions.

The impact of sepsis, delirium, and psychological distress on self-rated cognitive function in ICU survivors-a prospective cohort study.

BACKGROUND: Many intensive care unit (ICU) survivors develop psychological problems and cognitive impairment. The relation between sepsis, delirium, and later cognitive problems is not fully elucidated, and the impact of psychological symptoms on cognitive function is poorly studied in ICU survivors. The primary aim of this study was to examine the relationship between sepsis, ICU delirium, and later self-rated cognitive function. A second aim was to investigate the association between psychological problems and self-rated cognitive function 3 months after the ICU stay. METHODS: Patients staying more than 24 h at the general ICU at the Karolinska University Hospital Solna, Stockholm, Sweden, were screened for delirium with the Confusion Assessment Method-ICU (CAM-ICU) during their ICU stay. Sepsis incidence and severity were recorded. Three months later, 216 patients received the Cognitive Failures Questionnaire (CFQ), Hospital Anxiety and Depression Scale (HADS), and Post-Traumatic Stress Symptoms-10 (PTSS-10) questionnaires via postal mail. RESULTS: One hundred twenty-five patients (60%) responded to all questionnaires. Among respondents, the incidence of severe sepsis or septic shock was 42%. The overall incidence of delirium was 34%. Patients with severe sepsis/septic shock had a higher incidence of delirium, with an odds ratio (OR) of 3.7 (95% confidence interval (CI), 1.7-8.1). Self-rated cognitive problems 3 months post-ICU were found in 58% of the patients. We did not find any association between sepsis or delirium and late self-rated cognitive function. However, there was a correlation between psychological symptoms and self-rated cognitive function, with the strongest correlation between PTSS-10 scores and CFQ scores (r = 0.53; p < 0.001). CONCLUSIONS: ICU delirium is more common in severely septic/septic shock patients. In our cohort, neither severe sepsis nor ICU delirium was associated with self-rated cognitive function 3 months after the ICU stay. Ongoing psychological symptoms, particularly post-traumatic stress was associated with worse self-rated cognitive function. Psychological symptoms need to be taken into account when assessing cognitive function in ICU survivors.

Early psychological screening of intensive care unit survivors: a prospective cohort study.

BACKGROUND: A majority of patients survive their episode of critical illness but up to 30% of patients suffer from psychological problems such as post-traumatic stress, anxiety and depression in the year after intensive care unit (ICU) stay. A method to identify discharged patients at risk for adverse psychological outcome would be helpful in the triage for ICU follow-up and could enable early intervention. The aim of this study was to evaluate whether early screening with validated questionnaires after ICU discharge can identify patients at risk for symptoms of post-traumatic stress, anxiety and depression 3 months after ICU stay. METHODS: We performed a prospective observational cohort study in the general ICU at the Karolinska University Hospital Solna, Stockholm, Sweden. All adult patients surviving ≥ 24 hours in the ICU in a 9-month period were eligible for inclusion. Patients with mental disability, serious auditory and visual disorder, aphasia or who were unable to understand Swedish were excluded. One hundred and thirty-two patients were included and visited by a follow-up nurse within 1 week after ICU discharge. The Hospital Anxiety and Depression Scale (HADS) and the Post-Traumatic Stress Symptoms Checklist-10 (PTSS-10) were administered. Three months after ICU discharge the patients received the same questionnaires by postal mail. We assessed the predictive values of the questionnaires using the area under the receiver operating characteristic curve (AUROC). For correlation calculations, we used Spearman's rank correlation coefficient. Negative and positive predictive values for each questionnaire were calculated. RESULTS: Eighty-two patients returned the follow-up questionnaires. We found correlation between early and late scores and reasonable predictive precision regarding 3-month outcomes, with an AUROC of 0.90 for PTSS-10 part B, 0.80 for the HADS anxiety subscale and 0.75 for the HADS depression subscale. CONCLUSIONS: Symptoms of post-traumatic stress, anxiety and depression assessed 1 week after ICU stay correlate with 3-month psychological outcome. The HADS and PTSS-10 may be useful aids to identify ICU survivors at high risk for clinically significant symptoms of post-traumatic stress, anxiety and depression 3 months post ICU stay.

Diarrhea-associated hemolytic uremic syndrome with severe neurological manifestations treated with IgG depletion through immunoadsorption.

BACKGROUND: Diarrhea-associated hemolytic uremic syndrome (HUS) is characterized by acute kidney injury with microangiopathic hemolytic anemia and thrombocytopenia with a diarrhea prodrome, typically caused by Shiga-like toxin-producing Escherichia coli. Supportive management is generally recommended. CASE REPORT: A 58-year-old female with diarrhea-associated HUS developed delayed-onset severe neurological manifestations including coma, status epilepticus, and subcortical magnetic resonance imaging signal alterations. Rescue treatment with immunoglobulin (Ig)G depletion through immunoadsorption was followed by significant improvement in neurological and renal function. The patient recovered with only minimal sequelae. CONCLUSION: Delayed-onset neurological abnormalities may occur in diarrhea-associated HUS. Novel specific treatment options include IgG depletion through immunoadsorption. Severe clinical and imaging findings do not preclude a good outcome.

Neurally adjusted ventilatory assist feasibility during anaesthesia: A randomised crossover study of two anaesthetics in a large animal model.

BACKGROUND: Spontaneous breathing during mechanical ventilation improves gas exchange by redistribution of ventilation to dependent lung regions. Neurally adjusted ventilatory assist (NAVA) supports spontaneous breathing in proportion to the electrical activity of the diaphragm (EAdi). NAVA has never been used in the operating room and no studies have systematically addressed the influence of different anaesthetic drugs on EAdi. OBJECTIVES: The aim of this study was to test the feasibility of NAVA under sedation and anaesthesia with two commonly used anaesthetics, sevoflurane and propofol, with and without remifentanil, and to study their effects on EAdi and breathing mechanics. DESIGN: A crossover study with factorial design of NAVA during sedation and anaesthesia in pigs. SETTING: University basic science laboratory in Uppsala, Sweden, from March 2009 to February 2011. ANIMALS: Nine juvenile pigs were used for the experiment. INTERVENTIONS: The lungs were ventilated using NAVA while the animals were sedated and anaesthetised with continuous low-dose ketamine combined with sevoflurane and propofol, with and without remifentanil. MAIN OUTCOME MEASURES: During the last 5  min of each study period (total eight steps) EAdi, breathing pattern, blood gas analysis, neuromechanical efficiency (NME) and neuroventilatory efficiency (NVE) during NAVA were determined. RESULTS: EAdi was preserved and normoventilation was reached with both sevoflurane and propofol during sedation as well as anaesthesia. Tidal volume (Vt) was significantly lower with sevoflurane anaesthesia than with propofol. NME was significantly higher with sevoflurane than with propofol during anaesthesia with and without remifentanil. NVE was significantly higher with sevoflurane than with propofol during sedation and anaesthesia. CONCLUSION: NAVA is feasible during ketamine-propofol and ketamine-sevoflurane anaesthesia in pigs. Sevoflurane promotes lower Vt, and affects NME and NVE less than propofol. Our data warrant studies of NAVA in humans undergoing anaesthesia.

Early prediction of new-onset physical disability after intensive care unit stay: a preliminary instrument.

INTRODUCTION: Many intensive care unit (ICU) survivors suffer from physical disability for months after ICU stay. There is no structured method to identify patients at risk for such problems. The purpose of the study was to develop a method for early in-ICU prediction of the patient's individual risk for new-onset physical disability two months after ICU stay. METHODS: In total, 23 potential predictors for physical disability were assessed before individual ICU discharge. Two months after ICU discharge, out of 232 eligible patients, 148 ICU survivors (64%) completed the activity of daily living (ADL) staircase questionnaire to determine new-onset physical disability. RESULTS: A total of 95% percent of patients had no ADL reduction prior to ICU admission. 47% (n = 69) of questionnaire responders suffered from worsened ADL. We identified four independent predictors for new-onset physical disability: Low educational level (odds ratio (OR) =6.8), impaired core stability (OR = 4.6), fractures (OR = 4.5) and ICU length of stay longer than 2 days (OR = 2.6). The predictors were included in a screening instrument. The regression coefficient of each predictor was transformed into a risk score. The sum of risk scores was related to a predicted probability for physical disability in the individual patient. The cross-validated area under receiver operating characteristics curve (AUC) for the screening instrument was 0.80. CONCLUSIONS: Educational level is the single most important predictor for new-onset physical disability 2 months after ICU stay, followed by impaired core stability at ICU discharge, the presence of fractures and ICU stay longer than 2 days. A simple screening instrument based on these predictors can be used at ICU discharge to determine the risk for new-onset physical disability. This preliminary instrument may help clinicians to identify patients in need of support, but needs external validation prior to wider clinical use.

Inhaled isoflurane sedation during therapeutic hypothermia after cardiac arrest: a case series.

OBJECTIVE: Therapeutic hypothermia in the ICU requires mechanical ventilation and sedation. Hypothermia reduces the metabolism of commonly used IV sedatives. The use of long-acting sedative agents may confound neurologic assessment. Volatile anesthetics have been reported to provide protection against ischemia-reperfusion injury and have been safely used in the ICU to provide sedation in trials with shorter wake-up times. There are no clinical studies in this setting. We describe a case series and discuss potential benefits. DESIGN: Retrospective study. SETTINGS: Ten-bed ICU, university hospital. PATIENTS: Twelve patients resuscitated from cardiac arrest with Glasgow Coma Scale score less than or equal to 4. INTERVENTION: Isoflurane sedation with the AnaConDa during 24 hours therapeutic hypothermia, until rewarming. MEASUREMENTS AND MAIN RESULTS: Data were extracted from the computerized ICU chart/monitors, hospital and prehospital charts, and the national death index. Patients were 49-76 years old. Median return of spontaneous circulation was 14 minutes. Glasgow Coma Scale scores were assessed within 24 hours from reaching normal body temperature and compared with outcomes at 6 months: six patients had poor Glasgow Coma Scale scores (< 8) that remained low and all died before 6-month follow-up, whereas another six patients had high scores (> 8) and survived to 6 months with good Cerebral Performance Category. In the ICU, four of the survivors were directly extubated after rewarming while two were once more sedated due to pneumonia requiring invasive ventilator therapy. All patients required norepinephrine to maintain adequate mean arterial pressure. Isoflurane sedation was changed to midazolam in two nonsurviving patients because of hemodynamic instability, which persisted despite the change. CONCLUSIONS: Sedation with volatile anesthetics during therapeutic hypothermia may be a feasible short-acting option with potential postconditioning effects protecting vital organs from ischemia-reperfusion injury. Its measurability and insignificant drug accumulation could facilitate early neurologic assessment. Prospective clinical trials are warranted.