Predictors of New Onset Atrial Fibrillation Burden in the Critically Ill.

INTRODUCTION: Atrial fibrillation (AF) is common in the intensive care unit (ICU) setting and has been associated with adverse outcomes. In this context, there is increasing research interest in AF burden as a predictor of subsequent adverse events. However, the pathophysiology and drivers of AF burden in the ICU are poorly understood. This study sought to evaluate the predictors of AF burden in critical illness-associated new-onset AF (CI-NOAF). METHODS: Out of 7,030 admissions in a tertiary general ICU between December 2015 and September 2018, 309 patients developed CI-NOAF. AF burden was defined as the percentage of monitored time in AF, as extracted from hourly interpretations of continuous ECG monitoring. Low and high AF burden groups were defined relative to the median AF burden. Clinical, laboratory, and echocardiographic parameters were extracted, and multivariable modelling with binary logistic regression was performed to evaluate for independent associations with AF burden. RESULTS: The median AF burden was 7.0%. Factors associated with increased AF burden were age, dyslipidaemia, chronic kidney disease, increased creatinine, CHA2DS2-VASc score, ICU admission diagnosis category, amiodarone administration, and left atrial area (LAA). Factors associated with lower AF burden were previous alcohol excess, burden of ventilation, the use of inotropes/vasopressors, and beta blockers. On multivariate analysis, increased LAA, chronic kidney disease, and amiodarone use were independently associated with increased AF burden, whereas beta blocker use was associated with lower AF burden. CONCLUSION: Left atrial size and chronic cardiovascular comorbidities appear to be the primary drivers of CI-NOAF burden, whereas factors related to acute illness and critical care intervention paradoxically did not appear to be a substantial driver of arrhythmia burden. Further research is needed regarding drivers of AF and the efficacy of rhythm control intervention in this unique setting.

Critical illness associated new onset atrial fibrillation: subsequent atrial fibrillation diagnoses and other adverse outcomes.

AIMS: Amongst patients with critical illness associated new onset AF (CI-NOAF), the risk of subsequent atrial fibrillation (AF) diagnoses and other adverse outcomes is unknown, and the role for long-term anticoagulation is unclear. This study sought to determine the factors associated with subsequent AF diagnoses and other adverse outcomes in this cohort. METHODS AND RESULTS: Admissions to a tertiary general intensive care unit (ICU) between December 2015 and September 2018 were screened for AF episodes through hourly analysis of continuous ECG monitoring. Patients with a prior history of AF were excluded. AF burden was defined as the percentage of monitored ICU hours in AF. The primary endpoint was subsequent AF diagnoses, as collated from the statewide electronic medical records. Secondary endpoints included mortality, embolic events, MACE and subsequent anticoagulation. RESULTS: Of 7030 admissions with 509 303 h of monitoring data, 309 patients with CI-NOAF were identified, and 235 survived to discharge. Subsequent AF diagnoses were identified in 75 (31.9%) patients after a median of 413 days. Increased AF burden had the strongest independent association with AF recurrence (OR = 15.03, P = 0.002), followed by increased left atrial area (OR = 1.12, P = 0.01). Only 128 (54.5%) patients had their AF diagnosis acknowledged at ICU discharge, and 50 (21.3%) received anticoagulation at hospital discharge. CONCLUSION: CI-NOAF is often under-recognized, and subsequent AF diagnoses are common post-discharge. AF burden during ICU admission has a strong independent association with subsequent AF diagnoses. Left atrial size is also independently associated with subsequent AF.

Does mechanical threshold inspiratory muscle training promote recovery and improve outcomes in patients who are ventilator-dependent in the intensive care unit? The IMPROVE randomised trial.

BACKGROUND: In patients who are ventilator-dependent in the intensive care unit, inspiratory muscle training may improve inspiratory muscle strength and accelerate liberation from the ventilator, but optimal training parameters are yet to be established, and little is known about the impact of inspiratory muscle training on quality of life or dyspnoea. Thus, we sought to ascertain whether inspiratory muscle training, commenced while ventilator-dependent, would improve outcomes for patients invasively ventilated for 7 days or longer. METHODS: In this randomised trial with assessor blinding and intention-to-treat analysis, 70 participants (mechanically ventilated ≥7 days) were randomised to receive once-daily supervised high-intensity inspiratory muscle training with a mechanical threshold device in addition to usual care or to receive usual care (control). Primary outcomes were inspiratory muscle strength (maximum inspiratory pressure % predicted) and endurance (fatigue resistance index) at ventilator liberation and 1 week later. Secondary outcomes included quality of life (SF-36v2, EQ-5D), dyspnoea, physical function, duration of ventilation, and in-hospital mortality. RESULTS: Thirty-three participants were randomly allocated to the training group, and 37 to the control group. There were no statistically significant differences in strength (maximum inspiratory pressure) (95% confidence interval [CI]: -7.4 to 14.0) or endurance (fatigue resistance index) (95% CI: -0.003 to 0.436). Quality of life improved significantly more in the training group than in the control group (EQ-5D: 17.2; 95% CI: 1.3-33.0) (SF-36-PCS: 6.97; 95% CI: 1.96-12.00). Only the training group demonstrated significant reductions in dyspnoea (-1.5 at rest, -1.9 during exercise). There were no between-group differences in duration of ventilation or other measures. In-hospital mortality was higher in the control group than in the training group (9 vs 4, 24% vs 12%, p = 0.23). CONCLUSIONS: In patients who are ventilator-dependent, mechanical threshold loading inspiratory muscle training improves quality of life and dyspnoea, even in the absence of strength improvements or acceleration of ventilator liberation.

Inspiratory muscle training to enhance recovery from mechanical ventilation: a randomised trial.

BACKGROUND: In patients who have been mechanically ventilated, inspiratory muscles remain weak and fatigable following ventilatory weaning, which may contribute to dyspnoea and limited functional recovery. Inspiratory muscle training may improve inspiratory muscle strength and endurance following weaning, potentially improving dyspnoea and quality of life in this patient group. METHODS: We conducted a randomised trial with assessor-blinding and intention-to-treat analysis. Following 48 hours of successful weaning, 70 participants (mechanically ventilated ≥7 days) were randomised to receive inspiratory muscle training once daily 5 days/week for 2 weeks in addition to usual care, or usual care (control). Primary endpoints were inspiratory muscle strength and fatigue resistance index (FRI) 2 weeks following enrolment. Secondary endpoints included dyspnoea, physical function and quality of life, post-intensive care length of stay and in-hospital mortality. RESULTS: 34 participants were randomly allocated to the training group and 36 to control. The training group demonstrated greater improvements in inspiratory strength (training: 17%, control: 6%, mean difference: 11%, p=0.02). There were no statistically significant differences in FRI (0.03 vs 0.02, p=0.81), physical function (0.25 vs 0.25, p=0.97) or dyspnoea (-0.5 vs 0.2, p=0.22). Improvement in quality of life was greater in the training group (14% vs 2%, mean difference 12%, p=0.03). In-hospital mortality was higher in the training group (4 vs 0, 12% vs 0%, p=0.051). CONCLUSIONS: Inspiratory muscle training following successful weaning increases inspiratory muscle strength and quality of life, but we cannot confidently rule out an associated increased risk of in-hospital mortality. TRIAL REGISTRATION NUMBER: ACTRN12610001089022, results.

Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients.

BACKGROUND: Loss of circadian rhythms and reduced concentrations of endogenous melatonin are common in critically ill patients. After exogenous administration, supra-physiological concentrations in serum are only ephemeral, which may explain the absence of significant therapeutic effect on sleep. The aim of this study is to describe the pharmacokinetics of enteral melatonin in critically ill patients administered in a novel regimen aiming to simulate endogenous release. METHODS: Thirteen patients in the recovery phase of critical illness were randomised to receive enteral melatonin or placebo. In the melatonin group, a total of 6 mg was administered as solution through their feeding tube, commencing with a 3 mg loading dose at 9 pm and six subsequent 0.5 mg doses hourly. The placebo was administered using a similar regimen. Serial blood samples were taken and measured using a validated chromatographic method. The concentration-time data for serum melatonin concentrations were described using non-linear mixed-effects modelling. RESULTS: The observed concentrations in the melatonin patients were significantly higher than that observed in the placebo patients. The concentrations in the patients administered melatonin were also higher than endogenous melatonin concentrations previously reported in non-critically ill patients. The patients administered melatonin had a mean clearance, volume of distribution and absorption rate constant of melatonin was 55.2 L/h, 767 L and 0.76 h-1, respectively. CONCLUSIONS: Exogenous administration of melatonin with a loading dose of 3 mg followed by an hourly dose of 0.5 mg demonstrates good oral bioavailability and results in supra-physiological and sustained concentrations of serum melatonin during 12 h overnight.

Are interstitial fluid concentrations of meropenem equivalent to plasma concentrations in critically ill patients receiving continuous renal replacement therapy?

OBJECTIVES: To describe the interstitial fluid (ISF) and plasma pharmacokinetics of meropenem in patients on continuous venovenous haemodiafiltration (CVVHDF). PATIENTS AND METHODS: This was a prospective observational pharmacokinetic study. Meropenem (500 mg) was administered every 8 h. CVVHDF was targeted as a 2-3 L/h exchange using a polyacrylonitrile filter with a surface area of 1.05 m2 and a blood flow rate of 200 mL/min. Serial blood (pre- and post-filter), filtrate/dialysate and ISF concentrations were measured on 2 days of treatment (Profiles A and B). Subcutaneous tissue ISF concentrations were determined using microdialysis. RESULTS: A total of 384 samples were collected. During Profile A, the comparative median (IQR) ISF and plasma peak concentrations were 13.6 (12.0-16.8) and 40.7 (36.6-45.6) mg/L and the trough concentrations were 2.6 (2.4-3.4) and 4.9 (3.5-5.0) mg/L, respectively. During Profile B, the ISF trough concentrations increased by ∼40%. Meropenem ISF penetration was estimated at 63% (60%-69%) and 69% (65%-74%) for Profiles A and B, respectively, using comparative plasma and ISF AUCs. For Profile A, the plasma elimination t1/2 was 3.7 (3.3-4.0) h, the volume of distribution was 0.35 (0.25-0.46) L/kg, the total clearance was 4.1 (4.1-4.8) L/h and the CVVHDF clearance was 2.9 (2.7-3.1) L/h. CONCLUSIONS: This is the first known report of concurrent plasma and ISF concentrations of a meropenem antibiotic during CVVHDF. We observed that the ISF concentrations of meropenem were significantly lower than the plasma concentrations, although the present dose was appropriate for infections caused by intermediately susceptible pathogens (MIC≤4 mg/L).

A new marker of sepsis post burn injury?*.

OBJECTIVES: Accurate diagnosis of sepsis is difficult in patients post burn due to the large inflammatory response produced by the major insult. We aimed to estimate the values of serum N-terminal pro-B-type natriuretic peptide and procalcitonin and the changes in hemodynamic variables as markers of sepsis in critically ill burn patients. DESIGN: Prospective, observational study. SETTING: A quaternary-level university-affiliated ICU. PATIENTS: Fifty-four patients with burns to total body surface area of greater than or equal to 15%, intubated with no previous cardiovascular comorbidities, were enrolled. INTERVENTIONS: At admission, a FloTrac/Vigileo system was attached and daily blood samples taken from the arterial catheter. Infection surveillance was carried out daily with patients classified as septic/nonseptic according to American Burns Consensus criteria. MEASUREMENTS AND MAIN RESULTS: N-terminal pro-B-type natriuretic peptide, procalcitonin, and waveform analysis of changes in stroke volume index and systemic vascular resistance index were measured within the first 24 hours after burn and daily thereafter for the length of the ICU stay or until their first episode of sepsis. Prevalences of stroke volume variation less than 12% (normovolemia) with hypotension (systolic blood pressure < 90 mm Hg) were recorded. Patients with sepsis differed significantly from "no sepsis" for N-terminal pro-B-type natriuretic peptide, systemic vascular resistance index, and stroke volume index on days 3-7. Procalcitonin did not differ between sepsis and "no sepsis" except for day 3. Area under the receiver operating characteristic curves showed excellent discriminative power for B-type natriuretic peptide (p = 0.001; 95% CI, 0.99-1.00), systemic vascular resistance index (p < 0.001; 95% CI, 0.97-0.99), and stroke volume index (p < 0.01; 95% CI, 0.96-0.99) in predicting sepsis but not for procalcitonin (not significant; 95% CI, 0.29-0.46). A chi-square crosstab found that there was no relationship between hypotension with normovolemia (stroke volume variation < 12%) and sepsis. CONCLUSIONS: Serum N-terminal pro-B-type natriuretic peptide levels and certain hemodynamic changes can be used as an early indicator of sepsis in patients with burn injury. Procalcitonin did not assist in the early diagnosis of sepsis.

Augmented renal clearance in the ICU: results of a multicenter observational study of renal function in critically ill patients with normal plasma creatinine concentrations*.

OBJECTIVE: To describe the prevalence and natural history of augmented renal clearance in a cohort of recently admitted critically ill patients with normal plasma creatinine concentrations. DESIGN: Multicenter, prospective, observational study. SETTING: Four, tertiary-level, university-affiliated, ICUs in Australia, Singapore, Hong Kong, and Portugal. PATIENTS: Study participants had to have an expected ICU length of stay more than 24 hours, no evidence of absolute renal impairment (admission plasma creatinine < 120 µmol/L), and no history of prior renal replacement therapy or chronic kidney disease. Convenience sampling was used at each participating site. INTERVENTIONS: Eight-hour urinary creatinine clearances were collected daily, as the primary method of measuring renal function. Augmented renal clearance was defined by a creatinine clearance more than or equal to 130 mL/min/1.73 m. Additional demographic, physiological, therapeutic, and outcome data were recorded prospectively. MEASUREMENTS AND MAIN RESULTS: Nine hundred thirty-two patients were admitted to the participating ICUs over the study period, and 281 of which were recruited into the study, contributing 1,660 individual creatinine clearance measures. The mean age (95% CI) was 54.4 years (52.5-56.4 yr), Acute Physiology and Chronic Health Evaluation II score was 16 (15.2-16.7), and ICU mortality was 8.5%. Overall, 65.1% manifested augmented renal clearance on at least one occasion during the first seven study days; the majority (74%) of whom did so on more than or equal to 50% of their creatinine clearance measures. Using a mixed-effects model, the presence of augmented renal clearance on study day 1 strongly predicted (p = 0.019) sustained elevation of creatinine clearance in these patients over the first week in ICU. CONCLUSIONS: Augmented renal clearance appears to be a common finding in this patient group, with sustained elevation of creatinine clearance throughout the first week in ICU. Future studies should focus on the implications for accurate dosing of renally eliminated pharmaceuticals in patients with augmented renal clearance, in addition to the potential impact on individual clinical outcomes.

Toward improved surveillance: the impact of ventilator-associated complications on length of stay and antibiotic use in patients in intensive care units.

BACKGROUND: Hospitals and quality improvement agencies are vigorously focusing on reducing rates of hospital-acquired infection. Ventilator-associated pneumonia (VAP) is notoriously difficult to diagnose and surveillance is thwarted by the subjectivity of many components of the surveillance definition. Alternative surveillance strategies are needed. Ventilator-associated complications (VAC) is a simple, objective measure of respiratory deterioration. METHODS: VAC is defined by increases in fraction of inspired oxygen (FiO(2)) by ≥ 15% or positive end-expiratory pressure (PEEP) by ≥ 2.5 cm H(2)O lasting ≥ 2 days after stable or decreasing FiO(2) or PEEP lasting ≥ 2 days. We retrospectively assessed patients on mechanical ventilation for ≥ 48 hours in our study intensive care unit (ICU) using electronic medical record data. We analyzed the association between VAC and clinical diagnoses, ICU length of stay, duration of mechanical ventilation, antibiotic use, and mortality. RESULTS: We assessed 153 patients with VAC and 390 without VAC. VAC events were associated with significantly increased ICU length of stay, duration of mechanical ventilation, and consumption of broad-spectrum antibiotics but not with longer hospital stays or ICU mortality. CONCLUSIONS: Surveillance for VAP is subjective and labor intensive. VAC is an objective measure which can be readily obtained from electronic records. It is associated with adverse outcomes and increased broad-spectrum antibiotic usage. VAC may be a useful surveillance tool. The utility of VAC prevention bundles merits assessment.

Physical therapy for the critically ill in the ICU: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this systematic review was to review the evidence base for exercise in critically ill patients. DATA SOURCES AND STUDY SELECTION: Using keywords critical care and physical therapy and related synonyms, randomized controlled trials, meta-analyses, and systematic reviews were identified through electronic database searches and citation tracking. Clinical trials with outcomes of mortality, length of hospital and ICU stay, physical function and quality of life, muscle strength, and ventilator-free days were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers abstracted data and assessed quality independently. Effect sizes and 95% confidence intervals were calculated. From 3,126 screened abstracts, 10 randomized controlled trials and five reviews were found. The mean Physiotherapy Evidence Database score was 5.4. Overall there was a significant positive effect favoring physical therapy for the critically ill to improve the quality of life (g = 0.40, 95% confidence interval 0.08, 0.71), physical function (g = 0.46, 95% confidence interval 0.13, 0.78), peripheral muscle strength (g = 0.27, 95% confidence interval 0.02, 0.52), and respiratory muscle strength (g = 0.51, 95% confidence interval 0.12, 0.89). Length of hospital (g = -0.34, 95% confidence interval -0.53, -0.15) and ICU stay (g = -0.34, 95% confidence interval -0.51, -0.18) significantly decreased and ventilator-free days increased (g = 0.38, 95% confidence interval 0.16, 0.59) following physical therapy in the ICU. There was no effect on mortality. CONCLUSION: Physical therapy in the ICU appears to confer significant benefit in improving quality of life, physical function, peripheral and respiratory muscle strength, increasing ventilator-free days, and decreasing hospital and ICU stay. However, further controlled trials of better quality and larger sample sizes are required to verify the strength of these tentative associations.

Augmented renal clearance in septic and traumatized patients with normal plasma creatinine concentrations: identifying at-risk patients.

INTRODUCTION: Improved methods to optimize drug dosing in the critically ill are urgently needed. Traditional prescribing culture involves recognition of factors that mandate dose reduction (such as renal impairment), although optimizing drug exposure, through more frequent or augmented dosing, represents an evolving strategy. Elevated creatinine clearance (CLCR) has been associated with sub-therapeutic antibacterial concentrations in the critically ill, a concept termed augmented renal clearance (ARC). We aimed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients, while also examining demographic, physiological and illness severity characteristics that may help identify this phenomenon. METHODS: This prospective observational study was performed in a 30-bed tertiary level, university affiliated, adult intensive care unit. Consecutive traumatized and septic critically ill patients, receiving antibacterial therapy, with a plasma creatinine concentration ≤110 µmol/L, were eligible for enrolment. Pulse contour analysis (Vigileo / Flo Trac system, Edwards Lifesciences, Irvine, CA, USA), was used to provide continuous cardiac index (CI) assessment over a single six-hour dosing interval. Urinary CLCR measures were obtained concurrently. RESULTS: Seventy-one patients contributed data (sepsis n = 43, multi-trauma n = 28). Overall, 57.7% of the cohort manifested ARC, although there was a greater prevalence in trauma (85.7% versus 39.5%, P <0.001). In all patients, a weak correlation was noted between CI and CLCR (r = 0.346, P = 0.003). This was mostly driven by septic patients (r = 0.508, P = 0.001), as no correlation (r = -0.012, P = 0.951) was identified in trauma. Those manifesting ARC were younger (P <0.001), male (P = 0.012), with lower acute physiology and chronic health evaluation (APACHE) II (P= 0.008) and modified sequential organ failure assessment (SOFA) scores (P = 0.013), and higher cardiac indices (P = 0.013). In multivariate analysis, age ≤50 years, trauma, and a modified SOFA score ≤4, were identified as significant risk factors. These had greater utility in predicting ARC, compared with CI assessment alone. CONCLUSIONS: Diagnosis, illness severity and age, are likely to significantly influence renal drug elimination in the critically ill, and must be regularly considered in future study design and daily prescribing practice.

A comparison of CKD-EPI estimated glomerular filtration rate and measured creatinine clearance in recently admitted critically ill patients with normal plasma creatinine concentrations.

BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) has been widely integrated into clinical practice. Although useful in screening for CKD, its' application in critically ill patients with normal plasma creatinine concentrations remains uncertain. The aim of this study was to assess the performance of CKD-EPI eGFR in comparison to creatinine clearance (CLCR) in this setting. METHODS: This prospective observational study was performed in a tertiary level, university affiliated intensive care unit (ICU). Study participants had to have an expected ICU length of stay > 24 hours, a plasma creatinine concentration < 121 µmol/L, and no history of prior renal replacement therapy or CKD. CKD-EPI eGFR was compared against 8-hour measured urinary CLCR. Data capture occurred within 48 hours of admission. RESULTS: One hundred and ten patients (n = 110) were enrolled in the study. 63.6% were male, the mean age was 50.9 (16.9) years, 57.3% received invasive mechanical ventilation, and 30% required vasopressor support. The mean CLCR was 125 (45.1) ml/min/1.73 m(2), compared to a CKD-EPI eGFR of 101 (23.7) ml/min/1.73 m(2) (P < 0.001). Moderate correlation was evident (r = 0.72), although there was significant bias and imprecision (24.4 +/- 32.5 ml/min/1.73 m(2)). In those patients with a CKD-EPI eGFR between 60-119 ml/min/1.73 m(2) (n = 77), 41.6% displayed augmented renal clearance (CLCR ≥ 130 ml/min/1.73 m(2)), while 7.8% had a CLCR < 60 ml/min/1.73 m(2). CONCLUSIONS: These data suggest CKD-EPI eGFR and measured CLCR produce significantly disparate results when estimating renal function in this population. Clinicians should consider carefully which value they employ in clinical practice, particularly drug dose modification.

Remote care by telemedicine in the ICU: many models of care can be effective.

PURPOSE OF REVIEW: Telemedicine, by the use of audiovisual technologies, is increasingly being used to assist in patient care by ICUs unable to be staffed by consultant intensivists. This review discusses the recent evaluation of these services and their potential role in managing intensive care patients. RECENT FINDINGS: Models of care range from complete remote 24 h surveillance requiring direct video observation to a consultation liaison service only requiring conventional telephone links. There has been a rapid adoption of such services especially in North America where access to on-site intensive care specialists is limited for the volume of intensive care being undertaken. Early work suggests savings in terms of cost and length of stay with an improvement in compliance with care protocols. However, later work is not as supportive of such services, possibly related to differing care infrastructures and the organization of individual units. The key task is to ascertain the most appropriate service requirements that would assist in care for a given patient circumstance. SUMMARY: Clear benefits of ICU-telemedicine systems remain unclear but at least the systems appear safe. Formal reviews of the impacts and contribution of ICU telemedicine to processes of care, the effects on unit staffing, hospital organization, and the healthcare region are needed. However, ICU-telemedicine is available and being embraced by some, especially to deal with the tyranny of distance.

Early rehabilitation in sepsis: a prospective randomised controlled trial investigating functional and physiological outcomes The i-PERFORM Trial (Protocol Article).

BACKGROUND: Patients with sepsis syndromes in comparison to general intensive care patients can have worse outcomes for physical function, quality of life and survival. Early intensive care rehabilitation can improve the outcome in general Intensive Care Unit (ICU) patients, however no investigations have specifically looked at patients with sepsis syndromes. The 'i-PERFORM Trial' will investigate if early targeted rehabilitation is both safe and effective in patients with sepsis syndromes admitted to ICU. METHODS/DESIGN: A single-centred blinded randomized controlled trial will be conducted in Brisbane, Australia. Participants (n = 252) will include those ≥ 18 years, mechanically ventilated for ≥ 48 hours and diagnosed with a sepsis syndrome. Participants will be randomised to an intervention arm which will undergo an early targeted rehabilitation program according to the level of arousal, strength and cardiovascular stability and a control group which will receive normal care.The primary outcome measures will be physical function tests on discharge from ICU (The Acute Care Index of Function and The Physical Function ICU Test). Health-related quality of life will be measured using the Short Form-36 and the psychological component will be tested using The Hospital Anxiety and Depression Scale. Secondary measures will include inflammatory biomarkers; Interleukin-6, Interleukin-10 and Tumour Necrosis Factor-α, peripheral blood mitochondrial DNA content and lactate, fat free muscle mass, tissue oxygenation and microcirculatory flow. DISCUSSION: The 'i-PERFORM Trial' will determine whether early rehabilitation for patients with sepsis is effective at improving patient outcomes with functional and physiological parameters reflecting long and short-term effects of early exercise and the safety in its application in critical illness. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000808044.

Early Sequential Microcirculation Assessment In Shocked Patients as a Predictor of Outcome: A Prospective Observational Cohort Study.

OBJECTIVES: A dysfunctional microcirculation is universal in shock and is often dissociated from global hemodynamic parameters. Persistent microcirculatory derangements reflect ongoing tissue hypoperfusion and organ injury. The initial microcirculatory dysfunction and subsequent resolution could potentially guide therapy and predict outcomes. We evaluated the microcirculation early in a heterogenous shocked population. Microcirculatory resolution was correlated with measures of tissue perfusion and global hemodynamics. The relationship between the microcirculation over 24 h and outcome were evaluated. DESIGN: We prospectively recruited patients with all forms of shock, based on global hemodynamics and evidence of organ hypoperfusion. SETTING: A 30-bed adult intensive care unit (ICU). PATIENTS: Eighty-two shocked patients. MEASUREMENTS AND MAIN RESULTS: Following the diagnosis of shock, patients underwent a sublingual microcirculation examination using Sidestream Dark Field Imaging. The median age of patients was 66 years old (interquartile range [IQR] 54-71), with an Acute Physiology and Chronic Health Evaluation II of 27 (IQR 20-32). Microcirculatory parameters included Percentage Perfused Vessels (PPV), De Backer Score, and a heterogeneity index in patients with septic shock, according to the second consensus guidelines Additional parameters collected: temperature, heart rate and arterial pressure, cumulative fluid balance, and vasopressor use. Arterial blood samples were taken at the time of microcirculatory assessments, providing HCO3, lactate concentrations, PaO2, and PaCO2 measurements. A statistically significant improvement in PPV and the heterogeneity index was demonstrated. This improvement was mirrored by biomarkers of perfusion; however, the global hemodynamic parameter changes were not significantly different over the 24-h period. The early microcirculatory improvement was not predictive of an improvement in acute kidney injury, length of stay, ICU, or hospital mortality. CONCLUSIONS: Early sequential evaluation of the microcirculation in shocked patients, demonstrated statistically significant improvement in the PPV and microvascular heterogeneity with standard care. These improvements were mirrored by biomarkers of organ perfusion; however, the changes in global hemodynamics were not as pronounced in this early phase. Early improvement in the microcirculation did not predict clinical outcome.

Augmented creatinine clearance in traumatic brain injury.

BACKGROUND: Hypertonic saline and/or norepinephrine infusion are routinely used to achieve a desired cerebral perfusion pressure (CPP) in the management of traumatic brain injury (TBI). We hypothesized that creatinine clearances (CrCls) would be significantly augmented in this setting. METHODS: This was an observational cohort study in TBI patients older than 16 years with normal serum creatinine concentrations, requiring maintenance of CPP. Eight-hour urinary CrCl collections were performed while on and off active management. Demographic data, use of vasoactive medications, fluid balance, feeding regimen, and hemodynamic variables were recorded throughout the study period. Augmented CrCl was defined as >150 mL/min/1.73 m(2) in women and >160 mL/min/1.73 m(2) in men. RESULTS: Twenty patients were enrolled, and augmented clearances were demonstrated in 17 (85%). The mean maximum CrCl was 179 mL/min/1.73 m(2) while receiving CPP therapy (95% confidence interval [CI], 159-198), returning to a mean of 111 mL/min/1.73 m(2) (95% CI, 91-131; P < 0.001) when measured after discharge from the intensive care unit. The mean CrCl in the intensive care unit while not receiving CPP therapy was 150 mL/min/1.73 m(2) (95% CI, 134-167; P = 0.03). The mean time to reach peak CrCl while receiving active treatment was 4.7 days (95% CI, 3.0-6.4). In a multivariate analysis, norepinephrine use, saline loading, mean arterial blood pressure, and central venous pressure were associated with augmented CrCl on the day of measurement. CONCLUSIONS: Augmented CrCls are common in TBI patients receiving active management of CPP and persist even after discontinuation of such therapy. Further work is needed to clarify the impact of such clearances on renally excreted drugs in this setting.

Which ICU patients benefit most from inspiratory muscle training? Retrospective analysis of a randomized trial.

Background: Inspiratory muscle training (IMT) increases inspiratory muscle strength and improves quality of life in intensive care unit (ICU) patients who have been invasively mechanically ventilated for ≥7 days. The purpose of this study was to identify which patients benefit most from IMT following weaning from mechanical ventilation. Methods: Secondary analysis of a randomized trial of supervised daily IMT in 70 patients (mean age 59 years) in a 31-bed ICU was carried out. Changes in inspiratory muscle strength (maximum inspiratory pressure, MIP) between enrolment and 2 weeks (ΔMIP) were analyzed to compare the IMT group (71% male) and the control group (58% male). Linear regression models explored which factors at baseline were associated with ΔMIP. Results: Thirty-four participants were allocated to the IMT group where baseline MIP was associated with an increase in ΔMIP, significantly different from the control group (p = 0.025). The highest ΔMIP was associated with baseline MIP ≥ 28 cmH2O. In the IMT group, higher baseline quality of life (EQ5D) scores were associated with positive ΔMIP, significantly different from the control group (p = 0.029), with largest ΔMIP for those with EQ5D ≥ 40. Conclusions: Physiotherapists should target ICU patients with moderate inspiratory muscle weakness (MIP ≥28 cmH2O) and moderate to high quality of life (EQ5D>40) within 48 h of ventilatory weaning as ideal candidates for IMT following prolonged mechanical ventilation.