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Background: Emerging evidence indicates a relationship between glycemic variability during intensive care unit (ICU) admission and death. We assessed whether mean glucose, hypoglycemia occurrence, or premorbid glycemic control modified this relationship., Methods: In this retrospective, multicenter cohort study, we included adult patients admitted to five ICUs in Australia and Sweden with available preadmission glycated hemoglobin A1c (HbA1c) and three or more glucose readings. We calculated the glycemic lability index (GLI), a measure of glycemic variability, and the time-weighted average blood glucose (TWA-BG) from all glucose readings. We used logistic regression analysis with adjustment for hypoglycemia and admission characteristics to assess the independent association of GLI (above vs. below cohort median) and TWA-BG (above vs. below cohort median) with hospital mortality., Results: Among 2305 patients, 859 (37%) had diabetes, median GLI was 40 [mmol/L] 2 /h/week, median TWA-BG was 8.2 mmol/L, 171 (7%) developed hypoglycemia, and 371 (16%) died. The adjusted odds ratio for death was 1.61 (95% CI, 1.19-2.15; P = .002) for GLI above versus below median and 1.06 (95% CI, 0.80-1.41; P = .67) for TWA-BG above versus below median. The relationship between GLI and mortality was not modified by TWA-BG (P [interaction] = 0.66), a history of diabetes (P [interaction] = 0.89) or by HbA1c ≥52 mmol/mol (vs. <52 mmol/mol) (P [interaction] = 0.29)., Conclusion: In adult patients admitted to an ICU in Sweden and Australia, a high GLI was associated with increased hospital mortality irrespective of the level of mean glycemia, hypoglycemia occurrence, or premorbid glycemic control. These findings support the assessment of interventions to reduce glycemic variability during critical illness., (© 2021 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Objectives: The primary objective was to identify the proportion of patients on mechanical ventilation (MV) beyond day 10, the recently defined time of onset of Persistent Critical Illness (PerCI). The secondary objective was to identify underlying diagnoses, intensive care unit (ICU) based therapies, relevant complications, and outcomes of patients with PerCI., Subjects: 100 PerCI patients and 100 age, sex, mechanical ventilation for >24 h, acute physiology and chronic health score (APACHE III) and co-morbidity score-matched controls., Main Results: The maximum proportion of PerCI patients requiring invasive MV beyond day 10 was 66%. PerCI patients were more likely to have respiratory, septic, or neurosurgical admission diagnoses (p = .01). In the first 10 ICU days, they received multiple types of ICU-based treatments for longer duration and had a higher incidence rate of ventilator-associated pneumonia (VAP) (p = .008). Hospital discharge destination differed significantly (p≤.001), with greater mortality (34% vs. 22%) and discharge to chronic care facility (11% vs. 0%)., Conclusions: Mechanical ventilation beyond day 10 affected only two thirds of PerCI patients. However, VAP was a key complication in such patients. Discharge to chronic care facilities and hospital mortality were more common in PerCI patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) is common, although commonly used clinical diagnostic markers are imperfect. Intravenous fluid administration remains a cornerstone of therapy worldwide, but there is minimal evidence of efficacy for the use of fluid bolus therapy outside of specific circumstances, and emerging evidence associates fluid accumulation with worse renal outcomes and even increased mortality among critically ill patients. Artificial colloid solutions have been associated with harm, and chloride-rich solutions may adversely affect renal function. Large trials to provide guidance regarding the optimal fluid choices to prevent or ameliorate AKI, and promote renal recovery, are urgently required., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The renal histopathology of critically ill patients dying with acute kidney injury (AKI) in intensive care units of high income countries remains uncertain., Methods: Retrospective observational assessment of interobserver agreement in the reporting of renal post mortem histopathology, and the ability of pathologists blinded to the clinical context to independently identify the presence of pre-mortem AKI from digital images of histological sections from 34 critically ill patients dying in teaching hospitals in Australia and Canada., Results: We identified a heterogeneous cohort with a median age of 65 years (interquartile range [IQR], 56.5-77), APACHE II score of 27 (IQR, 19-33), and sepsis as the most common admission diagnosis (12/34; 35%). The most common proximate causes of death were cardiovascular (19/34; 56%) and respiratory (7/34; 21%) failure. AKI was common, with 23 patients (68%) developing RIFLE-F AKI, and 21 patients (62%) receiving renal replacement therapy. Structured reporting for tubular inflammation showed excellent agreement (kappa = 1), but no other subdomain demonstrated better than moderate agreement (kappa < 0.6). Only fair agreement (55.9% of cases; kappa = 0.23) was demonstrated on the diagnosis of moderate to severe acute tubular necrosis (ATN). Pathologist A predicted RIFLE-I or worse AKI with the diagnosis of ATN, with an overall accuracy of 61.8%; pathologist B predicted AKI with an accuracy of 35.3%., Conclusions: Post mortem assessment of the renal histopathology in critically ill patients is neither robust nor reproducible; independent pathologists agree poorly on the diagnosis of ATN, and their structural assessment appears dissociated from ante-mortem renal function.

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention., Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT., Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L., Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Magnesium is frequently measured and administered in general intensive care unit patients. However, magnesium status, its association with outcomes, and therapeutic utility in such patients are unclear. We performed a systematic review of the relevant literature to define current knowledge in this field., Materials and Methods: We searched MEDLINE, CENTRAL, and EMBASE from 1975 to July 2014 for adult English language articles excluding obstetric, non-intensive care unit based, and specific population (poisoning, cardiothoracic, and neurosurgery) studies. We identified articles on magnesium measurement, associations, and therapy. We calculated pooled effect estimates from reported adjusted risk estimates., Results: We identified 34 relevant studies. Total serum total magnesium was the most commonly measure of magnesium status. Risk of mortality was significantly increased with hypomagnesemia (odds ratio, 1.85; 95% confidence interval, 1.31-2.60). No consistent associations existed between magnesemia or magnesium administration and any other outcomes., Conclusions: Total serum magnesium levels are generally used to estimate magnesium status in critical illness. Hypomagnesemia appears associated with greater risk of mortality, but the efficacy of magnesium administration is open to challenge., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Fluid bolus therapy (FBT) is common in critically ill patients. With the exception of use in patients with traumatic brain injury, FBT with human albumin solution (HAS) appears safe and perhaps superior in severe sepsis., Objective: To determine the physiological effects of FBT with 4% v 20% HAS., Design, Setting and Participants: A retrospective observational study of 202 critically ill patients receiving FBT with HAS in a tertiary intensive care unit between April 2012 and March 2013., Methods: FBT was instituted with 4% or 20% HAS, according to clinician preference., Main Outcome Measures: We compared biochemical and haemodynamic data between groups at baseline and at 1, 2 and 4 hours after FBT., Results: Patients who had received 20% HAS had more liver disease, a greater need for renal replacement therapy and higher Acute Physiology and Chronic Health Evaluation III scores on admission. Patients who had received 4% HAS received a median volume of 500 mL (interquartile range [IQR], 350-500 mL), compared with 100mL (IQR, 100- 200 mL) in the 20% HAS group (P < 0.0001); a median of 70 mmol v 10 mmol of sodium (P < 0.0001); and a median of 64 mmol v 2 mmol of chloride (P < 0.0001). There was a trend toward higher mean arterial pressures in the 20% group after FBT (78.2 mmHg v 76.4 mmHg, P = 0.03). There were no significant differences in the absolute or percentage change for any haemodynamic parameters. Serum biochemical test results were comparable with a non-significant signal of higher serum chloride and more negative base excess in patients receiving 4% HAS., Conclusions: Haemodynamically, FBT with 100mL of 20% HAS performs in an equivalent way to 500 mL of 4% HAS but delivers much less fluid, sodium and chloride.

Objective: To study the effect of stress hyperlactatemia on the association between stress hyperglycemia and mortality., Design: Retrospective cross-sectional observation study., Setting: Three ICUs using arterial blood gases with simultaneous glucose and lactate measurements during ICU stay., Patients: Cohort of 7,925 consecutive critically ill patients., Interventions: None., Measurements and Main Results: We analyzed 152,349 simultaneous measurements of glucose and lactate. We performed multivariable analysis to study the association of different metrics of glucose and lactate with hospital mortality. On day 1, first (p = 0.013), highest (p = 0.001), mean (p = 0.019), and time-weighted mean (p = 0.010) glucose levels were associated with increased mortality. A similar, but stronger, association was seen for corresponding lactate metrics (p < 0.0001 for all). However, once glucose and lactate metrics were entered into the multivariable logistic regression model simultaneously, all measures of glycemia ceased to be significantly associated with hospital mortality regardless of the metrics being used (first, highest, mean, time-weighed; p > 0.05 for all), whereas all lactate metrics remained associated with mortality (p < 0.0001 for all). In patients with at least one episode of moderate hypoglycemia (glucose ≤ 3.9 mmol/L), glucose metrics were not associated with mortality when studied separately (p > 0.05 for all), whereas lactate was (p < 0.05 for all), but when incorporated into a model simultaneously, highest glucose on day 1 was associated with mortality (p< 0.05), but not other glucose metrics (p > 0.05), whereas all lactate metrics remained associated with mortality (p < 0.05 for all)., Conclusions: Stress hyperlactatemia modifies the relationship between hyperglycemia and mortality. There is no independent association between hyperglycemia and mortality once lactate levels are considered.

Background: Different molecular forms of urinary neutrophil gelatinase-associated lipocalin (NGAL) have recently been discovered. We aimed to explore the nature, source and discriminatory value of urinary NGAL in intensive care unit (ICU) patients., Methods: We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGAL(E1) and uNGAL(E2)] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of >25 μmol/L., Measurements and Main Results: Bland-Altman analysis demonstrated that, despite correlating well (r = 0.988), uNGAL and uNGAL(E1) were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95% CI 82.03-450.44 ng/mg creatinine; limits of agreement: -1,573.86 to 2,106.32 ng/mg creatinine). At best, urinary forms of NGAL are fair (area under the receiver operating characteristic [AUROC] ≤0.799) predictors of renal or patient outcome; most perform significantly worse. The 44 patients with a primarily monomeric source of uNGAL had higher pNGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001), remaining significant following Bonferroni correction., Conclusions: uNGAL is not a useful predictor of outcome in this ICU population. uNGAL patterns may predict distinct clinical phenotypes. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker.

Purpose: Oxygen (O2) is the most common therapy in mechanically ventilated patients, but targets and dose are poorly understood. We aimed to describe current O2 administration and titration in such patients in an academic intensive care unit., Materials and Methods: In consecutive ventilated (>48 hours) patients we prospectively obtained fraction of inspired O2 (FiO2), pulse oximetry O2 saturation (SpO2) and arterial O2 tension (PaO2) every 6 hours. We calculated the amount of excess O2 delivery and the intensivists' response to hyperoxemia (SpO2>98%)., Results: During 358 mechanical ventilation days in 51 critically ill patients, median calculated excess O2 delivery was 3472 L per patient. Patients spent most of their time with their SpO2>98% (59% [29-83]) and PaO2 between 80 and 120 mm Hg (59% [38-72]). In addition, 50% of all observations showed hyperoxemia and 4% severe hyperoxemia (PaO2>202.5 mm Hg). Moreover, 71% of the calculated total excess 263,841 L of O2 was delivered when the Fio2 was 0.3 to 0.5. When hyperoxemia occurred with an Fio2 between 0.3 and 0.4, for 88% of episodes, no Fio2 adjustments were made., Conclusions: Excess O2 delivery and liberal O2 therapy were common in mechanically ventilated patients. Current O2 therapy practice may be suboptimal and further investigations are warranted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Monitoring of fluid balance (FB) can be achieved by subtracting recorded fluid output from input or by measuring changes in body weight (BW). The latter approach is difficult in the critically ill. Recently, hospital beds have become available with the ability to directly weigh patients in the intensive care unit (ICU) patients directly. We sought to compare FB estimates obtained by these 2 methods in a cohort of critically ill patients., Materials and Methods: Between November 2010 and May 2011, all patients admitted in our ICU for more than 2 consecutive days and nursed on a Hill-Rom (Batesville, Ind) Total Care bed were weighed daily at midnight hours. Fluids charting was done by electronic spreadsheet with automated 24 hours calculation. Differences in BW and FB between 2 consecutive days were compared using correlation and Bland-Altman analysis. Corrections for unmeasured fluids losses were performed using a predetermined formula based on peak temperature and intubation status., Results: We obtained complete data in 160 (31%) of 504 admissions exceeding 2 days (153 patients) resulting in 435 data points. The change in BW over 24 hours and FB for the same period was only weakly correlated before (r = 0.34; P < .001; Fig. 1) or after correction for insensible fluid losses (r = 0.34; P < .001). On Bland-Altman plot, the mean bias was small (0.07 kg), but the 95% limits of agreement, very large (-5.8 and 6.0 kg). The lack of agreement increased with the magnitude of the changes., Conclusion: Obtaining daily weights in ICU patients proved difficult. Compliance was poor. The correlation between changes in BWs and FB was weak. Further studies are required to establish if accurate and reproducible daily weighing of ICU patients is feasible., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose of Review: Successful renal recovery is a key goal of patient management during acute kidney injury in critically ill patients. However, limited information exists to guide clinicians as to what interventions might either decrease or increase the likelihood of renal recovery and especially renal recovery to dialysis independence. The purpose of this review is to analyse recent data and help clinicians with relevant therapeutic choices., Recent Findings: Two large trials, the Acute Renal Failure Trial Network (ATN) and Randomized Evaluation of Normal versus Augmented Level Renal Replacement Therapy (RENAL), provide important evidence on the possible impact of choice of renal replacement therapy on renal recovery to dialysis independence. In the ATN trial in which intermittent haemodialysis (IHD) was delivered 5077 times, continued dialysis dependence by day 28 occurred in 45.2% of survivors, whereas in the RENAL study in which IHD was used 314 times, dialysis dependence at 28 days was 13.3%. These striking differences in favour of using continuous renal replacement therapy are supported by observational studies and a randomized controlled trial. Similarly the association of a positive fluid balance with poor outcomes has now been supported by multiple observational studies and multivariable logistic regression analysis. Both use of IHD and a positive fluid balance can delay renal recovery., Summary: Available evidence from randomized controlled trials and comparative analysis of their results as well as data from large observational studies suggest that the avoidance of IHD and of a positive fluid balance are likely to increase the speed of renal recovery and may prevent end-stage renal failure in selected high-risk patients with acute kidney injury.

Objective: To perform a meta-analysis of all relevant randomized controlled trials assessing the effect of erythropoiesis-stimulating agents (ESAs) in critically ill trauma patients. Background: ESAs have effects beyond erythropoiesis. The administration of the ESA epoetin alfa to critically ill trauma patients has been associated with a reduction in mortality. Methods: We performed a systematic review and meta-analysis with trial sequential analysis. We searched Medline, Medline in Process, and other nonindexed citations, EMBASE, and the Cochrane Database from inception until September 9, 2015, for randomized controlled trials comparing ESAs to placebo (or no ESA). Results: We identified 9 eligible studies that randomly assigned 2607 critically ill patients after trauma to an ESA or placebo (or no ESA). Compared with placebo (or no ESA), ESA therapy was associated with a substantial reduction in mortality [risk ratio (RR) 0.63, 95% confidence interval (CI) 0.49–0.79, P = 0.0001, I2 = 0%). In patients with traumatic brain injury, ESA therapy did not increase the number of patients surviving with moderate disability or good recovery (RR 1.00, 95% CI 0.88–1.15, P = 0.95, I2 = 0%). With the dosing regimens employed in the included studies, ESA therapy did not increase the risk of lower limb proximal deep venous thrombosis (RR 0.97, 95% CI 0.72–1.29, P = 0.78, I2 = 0%). Conclusions: The administration of ESAs to critically ill trauma patients is associated with a significant improvement in mortality without an increase in the rate of lower limb proximal deep venous thrombosis. Given the worldwide public health significance of these findings research to validate or refute them is required. [ABSTRACT FROM AUTHOR]

Objectives: To assess the feasibility and satety ot a conservative approach to oxygen therapy in mechanically ventilated ICU patients. Design: Pilot prospective before-and-after study. Setting: A 22-bed multidisciplinary ICU of a tertiary care hospital in Australia. Patients: A total of 105 adult (18 years old or older) patients required mechanical ventilation for more than 48 hours: 51 patients during the "conventional" before period and 54 after a change to "conservative" oxygen therapy. Interventions: Implementation of a conservative approach to oxygen therapy (target Spo2 of 90-92%). Measurements and Main Results: We collected 3,169 datasets on 799 mechanical ventilation days. During conservative oxygen therapy the median time-weighted average Spo2 on mechanical ventilation was 95.5% (interquartile range, 94.0-97.3) versus 98.4% (973-99.1) (p< 0.001) during conventional therapy. The median Pao2 was 83 torr (71-94) versus 107 torr (94-131) (p < 0.001) with a change to a median Fio2 of 0.27 (0.24-0.30) versus 0.40 (0.35-0.44) (p < 0.001). Conservative oxygen therapy decreased the median total amount of oxygen delivered during mechanical ventilation by about two thirds (15,580 L [8,263-29,351 L] vs 5,1 22L [1,837-10,499 L]; p < 0.001). The evolution of the Pao2/Fio2 ratio was similar during the two periods, and there were no difference in any other biochemical or clinical outcomes. Conclusions: Conservative oxygen therapy in mechanically ventilated ICU patients was feasible and free of adverse biochemical, physiological, or clinical outcomes while allowing a marked decrease in excess oxygen exposure. Cur study supports the safety and feasibility of future pilot randomized controlled trials of conventional compared with conservative oxygen therapy. [ABSTRACT FROM AUTHOR]