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Background: Intensive care unit (ICU)-acquired weakness often develops in patients who are undergoing invasive mechanical ventilation. Early active mobilization may mitigate ICU-acquired weakness, increase survival, and reduce disability., Methods: We randomly assigned 750 adult patients in the ICU who were undergoing invasive mechanical ventilation to receive increased early mobilization (sedation minimization and daily physiotherapy) or usual care (the level of mobilization that was normally provided in each ICU). The primary outcome was the number of days that the patients were alive and out of the hospital at 180 days after randomization., Results: The median number of days that patients were alive and out of the hospital was 143 (interquartile range, 21 to 161) in the early-mobilization group and 145 days (interquartile range, 51 to 164) in the usual-care group (absolute difference, -2.0 days; 95% confidence interval [CI], -10 to 6; P = 0.62). The mean (±SD) daily duration of active mobilization was 20.8±14.6 minutes and 8.8±9.0 minutes in the two groups, respectively (difference, 12.0 minutes per day; 95% CI, 10.4 to 13.6). A total of 77% of the patients in both groups were able to stand by a median interval of 3 days and 5 days, respectively (difference, -2 days; 95% CI, -3.4 to -0.6). By day 180, death had occurred in 22.5% of the patients in the early-mobilization group and in 19.5% of those in the usual-care group (odds ratio, 1.15; 95% CI, 0.81 to 1.65). Among survivors, quality of life, activities of daily living, disability, cognitive function, and psychological function were similar in the two groups. Serious adverse events were reported in 7 patients in the early-mobilization group and in 1 patient in the usual-care group. Adverse events that were potentially due to mobilization (arrhythmias, altered blood pressure, and desaturation) were reported in 34 of 371 patients (9.2%) in the early-mobilization group and in 15 of 370 patients (4.1%) in the usual-care group (P = 0.005)., Conclusions: Among adults undergoing mechanical ventilation in the ICU, an increase in early active mobilization did not result in a significantly greater number of days that patients were alive and out of the hospital than did the usual level of mobilization in the ICU. The intervention was associated with increased adverse events. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; TEAM ClinicalTrials.gov number, NCT03133377.)., (Copyright © 2022 Massachusetts Medical Society.)

Background and Rationale: Beta-lactam antibiotics are largely administered by bolus dosing, despite displaying time-dependent pharmacokinetics and pharmacodynamics and there being a strong rationale for continuous administration. The randomised controlled trials conducted to date comparing the mode of betalactam administration have been inconclusive and limited by non-equivalent dosing, unblinded administration and small sample sizes., Objective: A multicentre, randomised controlled trial (the Beta-lactam Infusion Group [BLING] II study) is currently under way, comparing continuous infusion to standard bolus administration of beta-lactam antibiotics in critically ill patients, independent of dose., Design, Settings, Participants and Interventions: BLING II is a Phase IIB, double-blinded, randomised controlled trial recruiting 420 intensive care unit patients with severe sepsis to receive one of three beta-lactam study antibiotics (ticarcillin-clavulanate, piperacillin- tazobactam or meropenem) by either continuous infusion or intermittent bolus administration., Main Outcome Measures: The primary outcome is ICUfree days at Day 28. Secondary outcomes include 90-day survival, clinical cure 14 days after study antibiotic cessation, organ failure-free days at Day 14 and duration of bacteraemia., Results and Conclusions: The study started in July 2012 and will provide clinical evidence as to whether continuous infusion of beta-lactam antibiotics is superior to intermittent bolus administration in critically ill patients with severe sepsis. A Phase III study powered for a survival end point may be justified, based on the results of our study.

Objective: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008., Design: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development., Methods: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations., Results: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C)., Conclusions: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Objective: To determine the accuracy of International classification of diseases, 10th revision, Australian modification (ICD-10-AM) codes in identifying severe sepsis in patients admitted from the emergency department (ED)., Design, Setting and Participants: A retrospective cohort study of ED patients transferred to the intensive care unit of a tertiary hospital within 24 hours of leaving ED, 2000- 2006., Main Outcome Measures: Clinical diagnosis of severe sepsis compared with diagnosis-based code (DB-C) categories based on ICD-10-AM codes in the Emergency Department Information Systems (EDIS) and Hospital Morbidity Data System (HMDS); sensitivity, specificity, positive predictive value (PPV) and negative predictive value of these databases., Results: In the study period, 1645 patients were transferred to the ICU from the ED, of whom 254 had severe sepsis. Single discharge ICD-10-AM codes recorded in the EDIS and the principal ICD-10-AM codes recorded in the HMDS that fell into D-BC categories for sepsis, pneumonia, viscous perforation, peritonitis, cholecystitis or cholangitis had a PPV of 85.0% (95% CI, 78.4%-91.6%; 96/113) and 88.2% (95%CI, 72.6%-82.6%; 112/127), respectively. The respective sensitivity was 37.8% (95% CI, 31.8%-43.8%) (96/254) and 44.1% (95% CI, 38.0-50.2) (112/254). In contrast, ICD-10-AM codes in the HMDS that code for infection and organ dysfunction had a PPV of 33.5% (95% CI, 30.0%-37.0%; 227/677) and sensitivity of 89.4% (95% CI, 85.6%-93.2%; 227/254)., Conclusion: ICD-10-AM codes recorded in the EDIS or HMD had limited utility for identifying severe sepsis in patients admitted to ICU from the ED.

Introduction: During the first winter of exposure, the H1N1 2009 influenza virus placed considerable strain on intensive care unit (ICU) services in Australia and New Zealand (ANZ). We assessed the impact of the H1N1 2009 influenza virus on ICU services during the second (2010) winter, following the implementation of vaccination., Methods: A prospective, cohort study was conducted in all ANZ ICUs during the southern hemisphere winter of 2010. Data on demographic and clinical characteristics, including vaccination status and outcomes, were collected. The characteristics of patients admitted during the 2010 and 2009 seasons were compared., Results: From 1 June to 15 October 2010, there were 315 patients with confirmed influenza A, of whom 283 patients (90%) had H1N1 2009 (10.6 cases per million inhabitants; 95% confidence interval (CI), 9.4 to 11.9) which was an observed incidence of 33% of that in 2009 (P < 0.001). The maximum daily ICU occupancy was 2.4 beds (95% CI, 1.8 to 3) per million inhabitants in 2010 compared with 7.5 (95% CI, 6.5 to 8.6) in 2009, (P < 0.001). The onset of the epidemic in 2010 was delayed by five weeks compared with 2009. The clinical characteristics were similar in 2010 and 2009 with no difference in the age distribution, proportion of patients treated with mechanical ventilation, duration of ICU admission, or hospital mortality. Unlike 2009 the incidence of critical illness was significantly greater in New Zealand (18.8 cases per million inhabitants compared with 9 in Australia, P < 0.001). Of 170 patients with known vaccination status, 26 (15.3%) had been vaccinated against H1N1 2009., Conclusions: During the 2010 ANZ winter, the impact of H1N1 2009 on ICU services was still appreciable in Australia and substantial in New Zealand. Vaccination failure occurred.

Aim: Determine current resuscitation practices and outcomes in patients presenting to the emergency department (ED) with sepsis and hypoperfusion or septic shock in Australia and New Zealand (ANZ)., Methods: Three-month prospective, multi-centre, observational study of all adult patients with sepsis and hypoperfusion or septic shock in the ED of 32 ANZ tertiary-referral, metropolitan and rural hospitals., Results: 324 patients were enrolled (mean [SD] age 63.4 [19.2] years, APACHE II score 19.0 [8.2], 52.5% male). Pneumonia (n=138/324, 42.6%) and urinary tract infection (n=98/324, 30.2%) were the commonest sources of sepsis. Between ED presentation and 6hours post-enrolment (T6hrs), 44.4% (n=144/324) of patients received an intra-arterial catheter, 37% (n=120/324) a central venous catheter and 0% (n=0/324) a continuous central venous oxygen saturation (ScvO(2)) catheter. Between enrolment and T6hrs, 32.1% (n=104/324) received a vasopressor infusion, 7.4% (n=24/324) a red blood cell transfusion, 2.5% (n=8/324) a dobutamine infusion and 18.5% (n=60/324) invasive mechanical ventilation. Twenty patients (6.2%) were transferred from ED directly to the operating theatre, 36.4% (n=118/324) were admitted directly to ICU, 1.2% (n=4/324) died in the ED and 56.2% (n=182/324) were transferred to the hospital floor. Overall ICU admission rate was 52.4% (n=170/324). ICU and overall in-hospital mortality were 18.8% (n=32/170) and 23.1% (n=75/324) respectively. In-hospital mortality was not different between patients admitted to ICU (24.7%, n=42/170) and the hospital floor (21.4%, n=33/154)., Conclusions: Management of ANZ patients presenting to ED with sepsis does not routinely include protocolised, ScvO(2)-directed resuscitation. In-hospital mortality compares favourably with reported mortality in international sepsis trials and nationwide surveys of resuscitation practices.

Objective: To investigate the association between socioeconomic status (SES) and outcomes for seriously ill patients., Design and Setting: A retrospective cohort study based on data from an intensive care unit clinical database linked with data from the Western Australian hospital morbidity and mortality databases over a 16-year period (1987-2002)., Main Outcome Measures: In-hospital and long-term mortality., Results: Data on 15,619 seriously ill patients were analysed. The in-hospital mortality rate for all seriously ill patients was 14.8%, and the incidence of death after critical illness was 7.4 per 100 person-years (4.8 per 100 person-years after hospital discharge). Patients from the most socioeconomically disadvantaged areas were more likely to be younger, to be Indigenous, to live in a remote area, to be admitted non-electively, and to have more severe acute disease and comorbidities. SES was not significantly associated with in-hospital mortality, but long-term mortality was significantly higher in patients from the lowest SES group than in those from the highest SES group, after adjusting for age, ethnicity, comorbidities, severity of acute illness, and geographical accessibility to essential services (hazard ratio for death in lowest SES group v highest SES group was 1.21 [95% CI, 1.04-1.41]; P = 0.014). The attributable incidence of death after hospital discharge between patients from the lowest and highest SES groups was 1.0 per 100 person-years (95% CI, 0.3-1.6 per 100 person-years)., Conclusion: Lower SES was associated with worse long-term survival after critical illness over and above the background effects of age, acuity of acute illness, comorbidities, Indigenous status and geographical access to essential services.

Objective: To identify prognostic determinants of long-term survival for patients treated in intensive care units (ICUs) who survived to hospital discharge., Design: An ICU clinical cohort linked to state-wide hospital records and death registers., Setting and Patients: Adult patients admitted to a 22-bed ICU at a major teaching hospital in Perth, Western Australia, between 1987 and 2002 who survived to hospital discharge (n = 19,921) were followed-up until December 31, 2003., Measurements: The main outcome measures are crude and adjusted survival., Main Results: The risk of death in the first year after hospital discharge was high for patients who survived the ICU compared with the general population (standardized mortality rate [SMR] at 1 yr = 2.90, 95% confidence interval [CI] 2.73-3.08) and remained higher than the general population for every year during 15 yrs of follow up (SMR at 15 yrs = 2.01, 95% CI 1.64-2.46). Factors that were independently associated with survival during the first year were older age (hazard ratio [HR] = 4.09; 95% CI 3.20-5.23), severe comorbidity (HR = 5.23; 95% CI 4.25-6.43), ICU diagnostic group (HR range 2.20 to 8.95), new malignancy (HR = 4.60; 95% CI 3.68-5.76), high acute physiology score on admission (HR = 1.55; 95% CI 1.23-1.96), and peak number of organ failures (HR = 1.51; 95% CI 1.11-2.04). All of these factors were independently associated with subsequent survival for those patients who were alive 1 yr after discharge from the hospital with the addition of male gender (HR = 1.17; 95% CI 1.10-1.25) and prolonged length of stay in ICU (HR = 1.42; 95% CI 1.29-1.55)., Conclusions: Patients who survived an admission to the ICU have worse survival than the general population for at least 15 yrs. The factors that determine long-term survival include age, comorbidity, and primary diagnosis. Severity of illness was also associated with long-term survival and this suggests that an episode of critical illness, or its treatment, may shorten life-expectancy.

Bacterial pathogens possess an array of specific mechanisms that confer virulence and the capacity to avoid host defence mechanisms. Mechanisms of virulence are often mediated by the subversion of normal aspects of host biology. In this way the pathogen modifies host function so as to promote the pathogen's survival or proliferation. Such subversion is often mediated by the specific interaction of bacterial effector molecules with host encoded proteins and other molecules. The importance of these mechanisms for bacterial pathogens that cause infections leading to severe community-acquired infections is well established. In contrast, the importance of specialised mechanisms of virulence in the genesis of nosocomial bacterial infections, which occur in the context of local or systemic defects in host immune defences, is less well established. Specific mechanisms of bacterial resistance to host immunity might represent targets for therapeutic intervention. The clinical utility of such an approach for either prevention or treatment of bacterial infection, however, has not been determined.

Objectives: To use clinically accessible tools to determine unit-level and individual patient factors associated with sound levels and sleep disruption in a range of representative ICUs.Design: A cross-sectional, observational study.Setting: Australian and New Zealand ICUs.Patients: All patients 16 years or over occupying an ICU bed on one of two Point Prevalence study days in 2015.Interventions: Ambient sound was measured for 1 minute using an application downloaded to a personal mobile device. Bedside nurses also recorded the total time and number of awakening for each patient overnight.Measurements and Main Results: The study included 539 participants with sound level recorded using an application downloaded to a personal mobile device from 39 ICUs. Maximum and mean sound levels were 78 dB (SD, 9) and 62 dB (SD, 8), respectively. Maximum sound levels were higher in ICUs with a sleep policy or protocol compared with those without maximum sound levels 81 dB (95% CI, 79-83) versus 77 dB (95% CI, 77-78), mean difference 4 dB (95% CI, 0-2), p < 0.001. There was no significant difference in sound levels regardless of single room occupancy, mechanical ventilation status, or illness severity. Clinical nursing staff in all 39 ICUs were able to record sleep assessment in 15-minute intervals. The median time awake and number of prolonged disruptions were 3 hours (interquartile range, 1-4) and three (interquartile range, 2-5), respectively.Conclusions: Across a large number of ICUs, patients were exposed to high sound levels and substantial sleep disruption irrespective of factors including previous implementation of a sleep policy. Sound and sleep measurement using simple and accessible tools can facilitate future studies and could feasibly be implemented into clinical practice. [ABSTRACT FROM AUTHOR]