Haemodynamic changes during prone versus supine position in patients with COVID-19 acute respiratory distress syndrome.

BACKGROUND: Prone positioning improves oxygenation in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19. However, its haemodynamic effects are poorly understood. OBJECTIVES: The objective of this study was to investigate the acute haemodynamic changes associated with prone position in mechanically ventilated patients with COVID-19 ARDS. The primary objective was to describe changes in cardiac index with prone position. The secondary objectives were to describe changes in mean arterial pressure, FiO2, PaO2/FiO2 ratio, and oxygen delivery (DO2) with prone position. METHODS: We performed this cohort-embedded study in an Australian intensive care unit, between September and November 2021. We included adult patients with severe COVID-19 ARDS, requiring mechanical ventilation and prone positioning for respiratory failure. We placed patients in the prone position for 16 h per session. Using pulse contour technology, we collected haemodynamic data every 5 min for 2 h in the supine position and for 2 h in the prone position consecutively. RESULTS: We studied 18 patients. Cardiac index, stroke volume index, and mean arterial pressure increased significantly in the prone position compared to supine position. The mean cardiac index was higher in the prone group than in the supine group by 0.44 L/min/m2 (95% confidence interval, 0.24 to 0.63) (P < 0.001). FiO2 requirement decreased significantly in the prone position (P < 0.001), with a significant increase in PaO2/FiO2 ratio (P < 0.001). DO2 also increased significantly in the prone position, from a median DO2 of 597 mls O2/min (interquartile range, 504 to 931) in the supine position to 743 mls O2/min (interquartile range, 604 to 1075) in the prone position (P < 0.001). CONCLUSION: Prone position increased the cardiac index, mean arterial pressure, and DO2 in invasively ventilated patients with COVID-19 ARDS. These changes may contribute to improved tissue oxygenation and improved outcomes observed in trials of prone positioning.

Evaluating an inquiry-based learning program.

Inquiry-based learning (IBL) is a promising educational framework that is understudied in graduate medical education. To determine participant satisfaction and engagement with phases of an IBL postgraduate education program, a mixed-methods study collected data via survey statements and open-ended responses. The authors included participants attending an intensive care medicine (ICM) IBL program from May to November 2020. Quantitative outcomes included participants' satisfaction with the IBL format and impact of engagement with IBL on the learning experience. Qualitative outcomes explored determinants of engagement with IBL phases and the impact on the learning experience. Of 378 attendees, 167 submitted survey responses (44.2%). There was strong agreement relating to overall satisfaction (93.4%). Responses indicated engagement with "orientation" (94.6%), "conceptualization" (97.3%), "discussion" (91.1%), and "conclusion" (91.0%) but limited engagement with the "investigation" phase (48.1%). Greater engagement with IBL phases had positive impacts, with repeat attenders having clearer learning objectives (79.1% vs. 56.6%, P < 0.05) and enhanced learning through collaborative discussion (65.9% vs. 48.7%, P < 0.05). Qualitative analysis showed that ICM learners value active learning principles, clear objectives, and a safe environment to expand their "knowledge base." Sessions facilitated "clinically relevant learning," with application of theoretical knowledge. Learners transformed and "reframed their understanding," using the input of others' experiences. ICM learners were highly satisfied with the IBL format and reported valuable learning. Participants engaged strongly with all IBL phases except the investigation phase during the sessions. IBL facilitated learners' active construction of meaning, facilitating a constructivist approach to learning.NEW & NOTEWORTHY An inquiry-based learning (IBL) program was launched as part of a novel binational intensive care medicine education program. Postgraduate intensive care medicine practitioners participated in this education intervention, where facilitated group discussions explored core intensive care medicine concepts. Survey responses indicated overall satisfaction, engagement with the IBL format, and a constructivist approach to learning. This study provided new insights into the benefits and challenges of an IBL program in the context of practicing clinicians.

Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial.

BACKGROUND: Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown. METHODS: We conducted a pilot, single-dose, double-blind, randomized controlled trial. We enrolled patients with septic shock within 24 h of diagnosis. We randomly assigned them to receive a single mega-dose of NaAscorbate (30 g over 1 h followed by 30 g over 5 h) or placebo (vehicle). The primary outcome was the total 24 h urine output (UO) from the beginning of the study treatment. Secondary outcomes included the time course of the progressive cumulative UO, vasopressor dose, and sequential organ failure assessment (SOFA) score. RESULTS: We enrolled 30 patients (15 patients in each arm). The mean (95% confidence interval) total 24-h UO was 2056 (1520-2593) ml with placebo and 2948 (2181-3715) ml with NaAscorbate (mean difference 891.5, 95% confidence interval [- 2.1 to 1785.2], P = 0.051). Moreover, the progressive cumulative UO was greater over time on linear mixed modelling with NaAscorbate (P < 0.001). Vasopressor dose and SOFA score changes over time showed faster reductions with NaAscorbate (P < 0.001 and P = 0.042). The sodium level, however, increased more over time with NaAscorbate (P < 0.001). There was no statistical difference in other clinical outcomes. CONCLUSION: In patients with septic shock, mega-dose NaAscorbate did not significantly increase cumulative 24-h UO. However, it induced a significantly greater increase in UO and a greater reduction in vasopressor dose and SOFA score over time. One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12620000651987), Date registered June/5/2020.

Changes in SedLine-derived processed electroencephalographic parameters during hypothermia in patients undergoing cardiac surgery with cardiopulmonary bypass.

Objective: Processed electroencephalography (pEEG) is used to monitor depth-of-anesthesia during cardiopulmonary bypass (CPB). The SedLine device has been recently introduced for pEEG monitoring. However, the effect of hypothermia on its parameters during CPB is unknown. Accordingly, we aimed to investigate temperature-induced changes in SedLine-derived pEEG parameters during CPB. Design: Prospective observational study. Setting: Cardiac surgery operating theatre. Participants: 28 patients undergoing elective cardiac surgery with CPB. Interventions: We continuously measured patient state index (PSI), suppression ratio (SR), bilateral spectral edge frequency (SEF) and temperature. We used linear mixed modelling with fixed and random effects to study the interactions between pEEG parameters and core temperature. Measurements and main results: During CPB maintenance, the median temperature was 32.1°C [interquartile range (IQR): 29.8-33.6] at the end of cooling and 32.8°C (IQR: 30.1-34.0) at rewarming initiation. For each degree Celsius change in temperature during cooling and rewarming the PSI either decreased by 0.8 points [95% confidence interval (CI): 0.7-1.0; p < 0.001] or increased by 0.7 points (95% CI: 0.6-0.8; p < 0.001). The SR increased by 2.9 (95% CI: 2.3-3.4); p < 0.001) during cooling and decreased by 2.2 (95% CI: 1.7-2.7; p < 0.001) during rewarming. Changes in the SEF were not related to changes in temperature. Conclusions: During hypothermic CPB, temperature changes led to concordant changes in the PSI. The SR increased during cooling and decreased during rewarming. Clinicians using SedLine for depth-of-anesthesia monitoring should be aware of these effects when interpreting the PSI and SR values.

Sodium glucose co-transporter-2 inhibitors in intensive care unit patients with type 2 diabetes: a pilot case control study.

BACKGROUND: Sodium glucose co-transporter-2 (SGLT2) inhibitors improve long-term cardiovascular and renal outcomes in individuals with type 2 diabetes. However, the safety of SGLT2 inhibitors in ICU patients with type 2 diabetes is uncertain. We aimed to perform a pilot study to assess the relationship between empagliflozin therapy and biochemical, and clinical outcomes in such patients. METHODS: We included 18 ICU patients with type 2 diabetes receiving empagliflozin (10 mg daily) and insulin to target glucose range of 10-14 mmol/l according to our liberal glucose control protocol for patients with diabetes (treatment group). Treatment group patients were matched on age, glycated hemoglobin A1c, and ICU duration with 72 ICU patients with type 2 diabetes exposed to the same target glucose range but who did not receive empagliflozin (control group). We compared changes in electrolyte and acid-base parameters, hypoglycemia, ketoacidosis, worsening kidney function, urine culture findings, and hospital mortality between the groups. RESULTS: Median (IQR) maximum increase in sodium and chloride levels were 3 (1-10) mmol/l and 3 (2-8) mmol/l in the control group and 9 (3-12) mmol/l and 8 (3-10) mmol/l in the treatment group (P = 0.045 for sodium, P = 0.059 for chloride). We observed no differences in strong ion difference, pH or base excess. Overall, 6% developed hypoglycemia in each group. No patient in the treatment group and one patient in the control group developed ketoacidosis. Worsening kidney function occurred in 18% and 29% of treatment and control group patients, respectively (P = 0.54). Urine cultures were positive in 22% of treatment group patients and 13% of control group patients (P = 0.28). Overall, 17% of treatment group patients and 19% of control group patients died in hospital (P = 0.79). CONCLUSIONS: In our pilot study of ICU patients with type 2 diabetes, empagliflozin therapy was associated with increases in sodium and chloride levels but was not significantly associated with acid-base changes, hypoglycemia, ketoacidosis, worsening kidney function, bacteriuria, or mortality.

Characteristics and outcomes of surgical patients admitted to an overnight intensive recovery unit: A retrospective observational study.

Postoperative 'enhanced care' models that sit between critical care and ward-based care may allow for more cost-effective and efficient utilisation of resources for high-risk surgical patients. In this retrospective observational study, we describe an overnight intensive recovery model in a tertiary hospital, termed 'recovery high dependency unit', and the characteristics, treatment, disposition at discharge and in-hospital outcomes of patients admitted to this unit. We included all adult patients (≥18 years) admitted to the recovery high dependency unit for at least one hour between July 2017 and June 2020. Over this three-year period, 1257 patients were included in the study. The median length of stay in the recovery high dependency unit was 12.6 (interquartile range 9.1-15.9) hours and the median length of hospital stay was 8.3 (interquartile range 5.0-17.3) days. Hospital discharge data showed that 1027 (81.7%) patients were discharged home and that 37 (2.9%) patients died. Non-invasive ventilation was delivered to 59 (4.7%) patients and 290 (23.1%) required vasopressor support. A total of 164 patients (13.0%) were admitted to the intensive care unit following their recovery high dependency unit admission. Of the 1093 patients who were discharged to the ward, 70 patients (6.4%) had a medical emergency team call within 24 hours of discharge from the recovery high dependency unit. In this study of a recovery high dependency unit patient cohort, there was a relatively low need for intensive care unit admission postoperatively and a very low incidence of medical emergency team calls post-discharge to the ward. Other institutions may consider the introduction and evaluation of this model in the care of their higher risk surgical patients.

Glycemic control and blood gas sampling frequency during continuous glucose monitoring in the intensive care unit: A before-and-after study.

BACKGROUND: Whether subcutaneous continuous glucose monitoring (CGM) can safely replace intermittent arterial blood gas glucose analyses in intensive care unit (ICU) patients remains uncertain. We aimed to compare CGM to blood gas glucose values and assess whether CGM use reduces blood gas sampling frequency and glucose variability in ICU patients with type 2 diabetes managed with liberal glucose control. METHODS: We used the FreeStyle Libre CGM in 15 ICU patients and compared their blood glucose metrics with a pre-CGM control population of 105 ICU patients with type 2 diabetes. Both groups received insulin to target glucose range of 10-14 mmol/L. We used linear regression analysis adjusted for illness severity to assess the association of CGM use with blood gas sampling frequency and glucose variability. We used mean absolute relative difference (MARD) and Clarke error grid analysis to assess accuracy of matched CGM-blood glucose values overall, across glucose stata (<10, 10-14, >14 mmol/L), and over time (≤48, 48-96, >96 h). RESULTS: We analyzed 483 matched glucose values. Overall MARD was 11.5 (95% CI, 10.7-12.3)% with 99% of readings in Clarke zones A and B. MARD was 15.5% for glucose values <10 mmol/L, 11.1% at 10-14 mmol/L, and 11.4% >14 mmol/L. MARD was 13.8% in the first 48 h, 10.9% at 48-96 h, and 8.9% beyond 96 h. CGM use was associated with 30% reduction in blood gas sampling frequency. CGM use was not associated with glucose variability as determined by glycemic lability index or standard deviation of blood glucose. CONCLUSIONS: In our cohort of ICU patients with type 2 diabetes receiving liberal glycemic control, CGM showed acceptable accuracy and was associated with a reduction in blood gas sampling frequency without compromising glucose control. Lowest accuracy was observed at glucose values below 10 mmol/L and during the first 48 h of CGM use.

Subsegmental pulmonary embolism and anticoagulant therapy: the impact of clinical context.

BACKGROUND: Anticoagulation for subsegmental pulmonary embolism (SSPE) is controversial. AIM: To assess the impact of clinical context on anticoagulation and outcomes of SSPE. METHODS: We electronically searched computed tomography pulmonary angiogram reports to identify SSPE. We extracted demographic, risk factor, investigations and outcome data from the electronic medical record. We stratified patients according to anticoagulation and no anticoagulation. RESULTS: From 1 January 2017 to 31 December 2019, we identified 166 patients with SSPE in 5827 pulmonary angiogram reports. Of these, 123 (74%) received anticoagulation. Compared with non-anticoagulated patients, such patients had a different clinical context: higher rates of previous venous thromboembolism (11% vs 0%; P = 0.019), more recent surgery (26% vs 9%; P = 0.015), more elevated serum D-dimer (22% vs 5%; P = 0.004), more lung parenchymal abnormalities (76% vs 61%; P = 0.037) and were almost twice as likely to require inpatient care (76% vs 42%; P < 0.001). Such patients also had twice the all-cause mortality at 1 year (32% vs 16%). CONCLUSIONS: SSPE is diagnosed in almost 3% of pulmonary angiograms and is associated with high mortality, regardless of anticoagulation, due to coexistent disease processes rather than SSPE. Anticoagulation appears dominant but markedly affected by the clinical context of risk factors, alternative indications and illness severity. Thus, the controversy is partly artificial because anticoagulation after SSPE is clinically contextual with SSPE as only one of several factors.

Trajectory of plasma syndecan-1 and heparan sulphate during major surgery: A retrospective observational study.

BACKGROUND: Surgical trauma-induced inflammation during major surgery may disrupt endothelial integrity and affect plasma concentrations of glycocalyx constituents, such as syndecan-1 and heparan sulphate. To date, no studies have focused on their perioperative temporal changes. METHODS: As part of a trial, we obtained plasma and urine specimens sampled during the perioperative period in 72 patients undergoing major abdominal surgery. The plasma concentration of syndecan-1 and heparan sulphate was measured on five occasions, from baseline to the second postoperative day. Plasma and urinary creatinine and urinary syndecan-1 concentrations were measured before surgery and on the first postoperative morning. RESULTS: We observed three different temporal patterns of plasma syndecan-1 concentration. Group 1 'low' (64% of patients) showed only minor changes from baseline despite a median heparan sulphate increase of 67% (p < .005). Group 2 'increase' (21% of patients) showed a marked increase in median plasma syndecan-1 from 27 µg/L to 118 µg/L during the first postoperative day (p < .001) with a substantial (+670%; p < .005) increase in median plasma heparan sulphate from 279 to 2196 µg/L. Group 3 'high' (14% of patients) showed a constant elevation of plasma syndecan-1 to >100 µg/L, but low heparan sulphate levels. The plasma C-reactive protein concentration did not differ across the three groups and 90% of colon surgeries occurred in Group 1. Treatment with dexamethasone was similar across the three groups. Surgical blood loss, duration of surgery and liver resection were greatest in Group 2. CONCLUSION: Changes in syndecan-1 and heparan sulphate after surgery appear to show three different patterns, with the greatest increases in those patients with greater blood loss, more liver surgery and longer operations. These observations suggest that increases in syndecan-1 and heparan sulphate reflect the degree of surgical injury.

Effects of changes in inspired oxygen fraction on urinary oxygen tension measurements.

BACKGROUND: Continuous measurement of urinary PO2 (PuO2) is being applied to indirectly monitor renal medullary PO2. However, when applied to critically ill patients with shock, its measurement may be affected by changes in FiO2 and PaO2 and potential associated O2 diffusion between urine and ureteric or bladder tissue. We aimed to investigate PuO2 measurements in septic shock patients with a fiberoptic luminescence optode inserted into the urinary catheter lumen in relation to episodes of FiO2 change. We also evaluated medullary and urinary oxygen tension values in Merino ewes at two different FiO2 levels. RESULTS: In 10 human patients, there were 32 FiO2 decreases and 31 increases in FiO2. Median pre-decrease FiO2 was 0.36 [0.30, 0.39] and median post-decrease FiO2 was 0.30 [0.23, 0.30], p = 0.006. PaO2 levels decreased from 83 mmHg [77, 94] to 72 [62, 80] mmHg, p = 0.009. However, PuO2 was 23.2 mmHg [20.5, 29.0] before and 24.2 mmHg [20.6, 26.3] after the intervention (p = 0.56). The median pre-increase FiO2 was 0.30 [0.21, 0.30] and median post-increase FiO2 was 0.35 [0.30, 0.40], p = 0.008. PaO2 levels increased from 64 mmHg [58, 72 mmHg] to 71 mmHg [70, 100], p = 0.04. However, PuO2 was 25.0 mmHg [IQR: 20.7, 26.8] before and 24.3 mmHg [IQR: 20.7, 26.3] after the intervention (p = 0.65). A mixed linear regression model showed a weak correlation between the variation in PaO2 and the variation in PuO2 values. In 9 Merino ewes, when comparing oxygen tension levels between FiO2 of 0.21 and 0.40, medullary values did not differ (25.1 ± 13.4 mmHg vs. 27.9 ± 15.4 mmHg, respectively, p = 0.6766) and this was similar to urinary oxygen values (27.1 ± 6.17 mmHg vs. 29.7 ± 4.41 mmHg, respectively, p = 0.3192). CONCLUSIONS: Changes in FiO2 and PaO2 within the context of usual care did not affect PuO2. Our findings were supported by experimental data and suggest that PuO2 can be used as biomarker of medullary oxygenation irrespective of FiO2.

The relationship between Nephrocheck® test values, outcomes, and urinary output in critically ill patients at risk of acute kidney injury.

BACKGROUND: Nephrocheck® was approved for acute kidney injury (AKI) risk assessment in critically illness. However, new studies suggest that urinary concentration affects Nephrocheck® and previous studies did not provide data on urinary output (UO) at the time of measurement. METHODS: We performed a prospective cohort study of the Nephrocheck® in intensive care unit patients fulfilling standard inclusion criteria. The primary outcome was Stage 2 or 3 AKI defined by both UO and creatinine Kidney Disease Improving Global Outcomes (KDIGO) criteria in the subsequent 12 h. The secondary outcome was the relationship of UO with Nephrocheck® measurement. RESULTS: Among 98 patients, the primary outcome occurred in 53 (54.1%) overall, but in 23 (23.5%) by creatinine criteria alone. The median (interquartile range) Nephrocheck® in patients with subsequent Stage 2 or 3 AKI was greater than in Stage 1 or no-AKI patients (0.97 [0.48-1.99] vs. 0.46 [0.22-1.17]; p = .005). However, its area under the receiver characteristic curve was 0.66 (95% confidence interval [CI], 0.56-0.77). Moreover, Nephrocheck® was significantly and inversely correlated with UO (ρ = -.46, p < .001) at the time of measurement and, on a multivariable logistic regression, Nephrocheck® was not associated with subsequent Stage 2 or 3 AKI (OR 1.06 [95% CI, 0.74-1.53], p = .73). In contrast, the UO had an OR of 0.98 for each ml/h increase (95% CI, 0.97-1.00, p = .007). CONCLUSION: Nephrocheck®'s predictive performance was limited and its value was inversely correlated with UO. Nephrocheck® had no independent relationship with outcome once UO at measurement was considered.

Immediate Higher-Dose Prothrombin Complex Concentrate Without Fresh Frozen Plasma or Fibrinogen Concentrate for Significant Coagulopathic Cardiac Surgical Field Bleeding.

BACKGROUND: Treatment of significant coagulopathic cardiac surgical field bleeding with immediate higher-dose prothrombin complex concentrate (PCC) without fresh frozen plasma (FFP) or fibrinogen concentrate is unexplored. AIMS: To study characteristics, chest drainage, and clinical outcomes of patients with significant coagulopathic surgical field bleeding treated with immediate higher-dose (defined at >15 IU/kg based on factor IX) PCC without FFP or fibrinogen concentrate. METHODS: We screened sequential cardiac surgery patients. We reviewed electronic blood bank data, Australian Society of Cardiothoracic Surgery database information and anaesthetic, intensive care unit (ICU), ward and radiological charts and electronic data. We identified patients deemed by the operating surgeon to require treatment for significant coagulopathic surgical field bleeding who underwent immediate higher-dose PCC without FFP or fibrinogen concentrate. RESULTS: Among 168 patients, we identified 30 who underwent immediate higher-dose PCC without FFP or fibrinogen concentrate. Median age was 68 years, 23 were male, 17 underwent coronary artery bypass surgery and three underwent complex surgery (David procedure, redo mitral valve surgery, and redo thoraco-abdominal aneurysm repair). Median dose of PCC was 2,500 IU. In addition, 27% underwent platelets and one underwent cryoprecipitate. Chest drainage at 24 hours was 505 ml. Survival to hospital discharge was 100%. There were no cases of pulmonary embolism, stroke, or other thrombotic events. Stage 1 AKI occurred in one patient. CONCLUSION: In a pilot cohort of patients with significant coagulopathic surgical field bleeding, immediate higher-dose PCC without FFP or fibrinogen concentrate was feasible and had an acceptable efficacy and safety profile, which justifies future controlled studies.

The Effects of Targeted Changes in Systemic Blood Flow and Mean Arterial Pressure on Urine Oximetry During Cardiopulmonary Bypass.

OBJECTIVES: Poor medullary oxygenation is implicated in the evolution of acute kidney injury. The authors sought to determine if increasing systemic flow and mean arterial pressure could improve urine oxygen tension (PuO2) measured in the bladder, a surrogate of kidney medullary oxygenation, in patients undergoing on-pump cardiac surgery. DESIGN: Randomized crossover study. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty adult patients undergoing cardiopulmonary bypass (CPB) with expected cross-clamp time of >60 minutes and estimated glomerular filtration rate of >30 mL/min/1.73m2. INTERVENTIONS: Sequential 20-minute periods of 2 interventions: Intervention H ("High") or Intervention N ("Normal"). The order of interventions was determined by randomization. Intervention H: targeted CPB flow 3.0 L/min/m2 and mean arterial pressure (MAP) 80 mmHg. Intervention N: targeted CPB flow 2.4 L/min/m2 and MAP 65 mmHg. MEASUREMENTS AND MAIN RESULTS: PuO2 was measured by an oxygen sensor introduced into the bladder via a urinary catheter. Clear separation was achieved in CPB flow and MAP between intervention periods (p < 0.001 for group-time interaction). PuO2 during Intervention H was higher than during Intervention N (p < 0.001 for group-time interaction). After 17 minutes, PuO2 was statistically higher in Intervention H at each time point. There were no differences in markers of hemolysis between interventions. CONCLUSIONS: PuO2 was higher when systemic flow and MAP were increased during CPB. These findings suggest that PuO2 is responsive to changes in hemodynamics and that higher flow and pressure may improve medullary oxygenation.

Serum Creatinine Levels and Nephrocheck® Values With and Without Correction for Urine Dilution-A Multicenter Observational Study.

BACKGROUND: The Nephrocheck® test is a single-use cartridge designed to measure the concentrations of two novel cell-cycle arrest biomarkers of acute kidney injury, namely tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7). Correlations of serum creatine values and TIMP-2 and IGFBP7 with and without correction for urine dilution have not been previously undertaken in patients undergoing major abdominal surgery. We hypothesized that the Nephrocheck® values would be significantly different with and without correction for urine dilution in patients with elevated creatinine values post major abdominal surgery. METHODS: We performed a post hoc analysis of serum and urine specimens sampled preoperatively and postoperatively in 72 patients undergoing major abdominal surgery. Thirty samples were measured from patients with the greatest decrease and the greatest increase in postoperative serum creatinine values. Urine was analyzed with the Nephrocheck to predict the risk of acute kidney injury (AKIRisk™). We then examined the relationship between serum creatinine and the urinary excretion of TIMP-2 and IGFBP7 as measured by the Nephrocheck test. The AKIRisk between the groups with and without correction for urine dilution was assessed. RESULTS: The median perioperative change in serum creatinine in the two groups was -19% and +57%, respectively. The uncorrected median baseline AKIRisk decreased from 0.70 (25th-75th percentiles, 0.09-1.98) to 0.35 (0.19-0.57) (mg/L)2 in the first group and rose from 0.57 (0.22-1.53) to 0.85 (0.67-2.20) (mg/L)2 in the second group. However, when corrected for the squared urine dilution, the AKIRisk™ in patients with postoperative increases in serum creatinine was not indicative of kidney injury; the corrected AKIRisk was 8.0 (3.2-11.7) µg2/mmol2 before surgery vs.6.9 (5.3-11.0) µg2/mmol2 after the surgery (P = 0.69). CONCLUSION: In the setting of major abdominal surgery, after correction of TIMP-2 and IGFBP7 for urine dilution, the Nephrocheck AKIRisk scores were significantly different from the uncorrected values. These finding imply that the AKIRisk index is a function of urine flow in addition to an increased release of the biomarkers.

A pilot study of the pharmacokinetics of continuous magnesium infusion in critically ill patients.

Objective: The pharmacokinetics and haemodynamic effect of continuous magnesium infusion in non-cardiac intensive care unit (ICU) patients are poorly understood. We aimed to measure serum and urine magnesium levels during bolus and continuous infusion in critically ill adults, compare serum levels with those of a control population, and assess its haemodynamic effect. Design: Pharmacokinetic study Setting: A single tertiary adult ICU. Participants: Mechanically ventilated adults requiring vasopressor support. Intervention: A 10 mmol bolus of magnesium sulfate followed by 1.5-3 mmol/h infusion for 24 hours. Main outcome measures: The primary outcome was the change in total serum magnesium concentration. The main secondary outcome was mean arterial pressure (MAP)- adjusted vasopressor dose. Results: We matched 31 treated patients with 93 controls. Serum total magnesium concentration increased from a median 0.94 mmol/L (interquartile range [IQR], 0.83-1.10 mmol/L) to 1.38 mmol/L (IQR, 1.25-1.69 mmol/L; P < 0.001) and stabilised between a median 1.64 mmol/L (IQR, 1.38-1.88 mmol/L) at 7 hours and 1.77 mmol/L (IQR, 1.53-1.85 mmol/L) at 25 hours. This was significantly greater than in the control group (P < 0.001). The MAP-adjusted vasopressor dose decreased during magnesium infusion (P < 0.001). Conclusion: In critically ill patients, a magnesium sulfate bolus followed by continuous infusion achieved moderately elevated levels of total serum magnesium with a decrease in MAP-adjusted vasopressor dose. Trial registration number: ACTRN12619000925145.

The hemodynamic effects of warm versus room-temperature crystalloid fluid bolus therapy in post-cardiac surgery patients.

INTRODUCTION: The contribution of fluid temperature to the effect of crystalloid fluid bolus therapy (FBT) in post-cardiac surgery patients is unknown. We evaluated the hemodynamic effects of FBT with fluid warmed to 40°C (warm FBT) versus room-temperature fluid. METHODS: In this single centre prospective before-and-after study, we evaluated the effects of 500 ml of warm versus room-temperature compound sodium lactate administered over <30 minutes, in 50 cardiac surgery patients admitted to ICU. We recorded hemodynamics continuous before and for 30 minutes after the first FBT. We defined CI responsiveness (CI-R) as an CI increase >15% of baseline immediately after FBT and effect dissipation if the CI returned to <5% of baseline and MAP responsiveness as >10% increase and dissipation as return to <3 mmHg of baseline. RESULTS: Hypotension (56%) and low CI (40%) typically triggered FBT. Temperature decreased >0.3°C in 13 (52%) patients after room-temperature FBT versus 0 (0%) after warm FBT (p < 0.01). CI and MAP responsiveness was similar (16 [64%] versus 11 [44%], p = 0.15 and 15 [60%] versus 17 [68%], p = 0.77, respectively). Among CI responders, CI increased more with room-temperature FBT (+0.6 [IQR, 0.5-1.1] versus +0.5 [IQR, 0.4-0.6] L/min/m2, p = 0.01). However, dissipation was more common after room-temperature versus warm FBT (9/16 [56%] versus 1/11 [9%], p = 0.02). CONCLUSION: In postoperative cardiac surgery patients, warm FBT preserved core temperature and induced smaller but more sustained CI increases among responders. Fluid temperature appears to impact both core temperature and the duration of CI response.

Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: a systematic review and a component network meta-analysis.

We aimed to compare the effects of vitamin C, glucocorticoids, vitamin B1, combinations of these drugs, and placebo or usual care on longer-term mortality in adults with sepsis or septic shock. MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and WHO-ICTRP were searched. The final search was carried out on September 3rd, 2021. Multiple reviewers independently selected randomized controlled trials (RCTs) comparing very-high-dose vitamin C (≥ 12 g/day), high-dose vitamin C (< 12, ≥ 6 g/day), vitamin C (< 6 g/day), glucocorticoid (< 400 mg/day of hydrocortisone), vitamin B1, combinations of these drugs, and placebo/usual care. We performed random-effects network meta-analysis and, where applicable, a random-effects component network meta-analysis. We used the Confidence in Network Meta-Analysis framework to assess the degree of treatment effect certainty. The primary outcome was longer-term mortality (90-days to 1-year). Secondary outcomes were severity of organ dysfunction over 72 h, time to cessation of vasopressor therapy, and length of stay in intensive care unit (ICU). Forty-three RCTs (10,257 patients) were eligible. There were no significant differences in longer-term mortality between treatments and placebo/usual care or between treatments (10 RCTs, 7,096 patients, moderate to very-low-certainty). We did not find any evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay. Adding glucocorticoid to other treatments shortened duration of vasopressor therapy (incremental mean difference, - 29.8 h [95% CI - 44.1 to - 15.5]) and ICU stay (incremental mean difference, - 1.3 days [95% CI - 2.2 to - 0.3]). Metabolic resuscitation with vitamin C, glucocorticoids, vitamin B1, or combinations of these drugs was not significantly associated with a decrease in longer-term mortality.

A pilot, feasibility, randomised controlled trial of midodrine as adjunctive vasopressor for low-dose vasopressor-dependent hypotension in intensive care patients: The MAVERIC study.

PURPOSE: To assess the feasibility and physiological efficacy of adjunctive midodrine in patients with vasopressor-dependent hypotension. MATERIALS AND METHODS: This was a pilot, open label, randomised controlled trial. Patients were enrolled from two tertiary intensive care units on low dose intravenous vasopressor therapy for more than 24 h. We randomly assigned patients to receive either adjunctive midodrine (10 mg every 8 h) or usual care. The primary efficacy outcome was time to cessation of intravenous vasopressor therapy. Secondary outcomes included protocol compliance, ICU and hospital length of stay. RESULTS: We screened 381 patients over 22-months and enrolled 62 (32 in midodrine group, 30 in usual care group). Median time to cessation of vasopressor infusion was 16.5 h for midodrine vs 19 h for usual care (p = 0.22). Time in ICU (50 [25.50, 74.00] hours for midodrine v 59 [38.50, 93.25] hours for usual care, p = 0.14) and hospital length of stay (9 days vs. 7.5 days, p = 0.92) were similar. Protocol compliance was 96.9%. One patient ceased midodrine early due to symptomatic bradycardia. CONCLUSIONS: Adjunctive midodrine therapy was feasible with acceptable compliance, duration of therapy, and safety profile. However, at the chosen dose, there was no evidence of physiological or clinical efficacy.

A multicenter randomized clinical trial of pharmacological vitamin B1 administration to critically ill patients who develop hypophosphatemia during enteral nutrition (The THIAMINE 4 HYPOPHOSPHATEMIA trial).

BACKGROUND: Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group. METHOD: This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified. RESULTS: Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = -0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: -32 (-39, -26) vs. control: -24 (-31, -16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25). CONCLUSIONS: In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167).