Renin Levels and Angiotensin II Responsiveness in Vasopressor-Dependent Hypotension.

OBJECTIVES: The relationship between renin levels, exposure to renin-angiotensin system (RAS) inhibitors, angiotensin II (ANGII) responsiveness, and outcome in patients with vasopressor-dependent vasodilatory hypotension is unknown. DESIGN: We conducted a single-center prospective observational study to explore whether recent RAS inhibitor exposure affected baseline renin levels, whether baseline renin levels predicted ANGII responsiveness, and whether renin levels at 24 hours were associated with clinical outcomes. SETTING: An academic ICU in Melbourne, VIC, Australia. PATIENTS: Forty critically ill adults who received ANGII as the primary agent for vasopressor-dependent vasodilatory hypotension who were included in the Acute Renal effects of Angiotensin II Management in Shock study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After multivariable adjustment, recent exposure to a RAS inhibitor was independently associated with a relative increase in baseline renin levels by 198% (95% CI, 36-552%). The peak amount of ANGII required to achieve target mean arterial pressure was independently associated with baseline renin level (increase by 46% per ten-fold increase; 95% CI, 8-98%). Higher renin levels at 24 hours after ANGII initiation were independently associated with fewer days alive and free of continuous renal replacement therapy (CRRT) (-7 d per ten-fold increase; 95% CI, -12 to -1). CONCLUSIONS: In patients with vasopressor-dependent vasodilatory hypotension, recent RAS inhibitor exposure was associated with higher baseline renin levels. Such higher renin levels were then associated with decreased ANGII responsiveness. Higher renin levels at 24 hours despite ANGII infusion were associated with fewer days alive and CRRT-free. These preliminary findings emphasize the importance of the RAS and the role of renin as a biomarker in patients with vasopressor-dependent vasodilatory hypotension.

Carboxyhemoglobin in Cardiac Surgery Patients and Its Association with Risk Factors and Biomarkers of Hemolysis.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with hemolysis. Yet, there is no easily available and frequently measured marker to monitor this hemolysis. However, carboxyhemoglobin (CO-Hb), formed by the binding of carbon monoxide (a product of heme breakdown) to hemoglobin, may reflect such hemolysis. We hypothesized that CO-Hb might increase after cardiac surgery and show associations with operative risk factors and indirect markers for hemolysis. METHODS: We conducted a retrospective descriptive cohort study of data from on-pump cardiac surgery patients. We analyzed temporal changes in CO-Hb levels and applied a generalized linear model to assess patient characteristics associated with peak CO-Hb levels. Additionally, we examined their relationship with red blood cell (RBC) transfusion and bilirubin levels. RESULTS: We studied 38,487 CO-Hb measurements in 1735 patients. CO-Hb levels increased significantly after cardiac surgery, reaching a peak CO-Hb level 2.1 times higher than baseline ( P < .001) at a median of 17 hours after the initiation of surgery. Several factors were independently associated with higher peak CO-Hb, including age ( P < .001), preoperative respiratory disease ( P = .001), New York Heart Association Class IV ( P = .019), the number of packed RBC transfused ( P < .001), and the duration of CPB ( P = .002). Peak CO-Hb levels also significantly correlated with postoperative total bilirubin levels (Rho = 0.27, P < .001). CONCLUSIONS: CO-Hb may represent a readily obtainable and frequently measured biomarker that has a moderate association with known biomarkers of and risk factors for hemolysis in on-pump cardiac surgery patients. These findings have potential clinical implications and warrant further investigation.

Magnitude and time to peak oxygenation effect of prone positioning in ventilated adults with COVID-19 related acute hypoxemic respiratory failure.

BACKGROUND: Prone positioning may improve oxygenation in acute hypoxemic respiratory failure and was widely adopted in COVID-19 patients. However, the magnitude and timing of its peak oxygenation effect remain uncertain with the optimum dosage unknown. Therefore, we aimed to investigate the magnitude of the peak effect of prone positioning on the PaO2 :FiO2 ratio during prone and secondly, the time to peak oxygenation. METHODS: Multi-centre, observational study of invasively ventilated adults with acute hypoxemic respiratory failure secondary to COVID-19 treated with prone positioning. Baseline characteristics, prone positioning and patient outcome data were collected. All arterial blood gas (ABG) data during supine, prone and after return to supine position were analysed. The magnitude of peak PaO2 :FiO2 ratio effect and time to peak PaO2 :FIO2 ratio effect was measured. RESULTS: We studied 220 patients (mean age 54 years) and 548 prone episodes. Prone positioning was applied for a mean (±SD) 3 (±2) times and 16 (±3) hours per episode. Pre-proning PaO2 :FIO2 ratio was 137 (±49) for all prone episodes. During the first episode. the mean PaO2 :FIO2 ratio increased from 125 to a peak of 196 (p < .001). Peak effect was achieved during the first episode, after 9 (±5) hours in prone position and maintained until return to supine position. CONCLUSIONS: In ventilated adults with COVID-19 acute hypoxemic respiratory failure, peak PaO2 :FIO2 ratio effect occurred during the first prone positioning episode and after 9 h. Subsequent episodes also improved oxygenation but with diminished effect on PaO2 :FIO2 ratio. This information can help guide the number and duration of prone positioning episodes.

Perfusate hemoglobin during normothermic liver machine perfusion as biomarker of early allograft dysfunction: A pilot study.

BACKGROUND: Normothermic machine perfusion (NMP) aims to reduce ischemia-reperfusion injury in donor livers and its clinical manifestation, early allograft dysfunction (EAD) by maintaining perfusion and oxygenation. However, there is limited data on which NMP perfusate biomarkers might be associated with such EAD and the role of perfusate hemoglobin has not been assessed. METHODS: We performed a pilot retrospective analysis of adult donor livers undergoing NMP between 2020 and 2022 at our center. NMP was commenced at the recipient hospital after initial static cold storage. All NMP circuits were primed in the same manner according to the manufacturer's instructions. Livers were stratified by initial perfusate hemoglobin below (≤5.2 mmol/L) or above (>5.2 mmol/L) the median. The association between hemoglobin levels and EAD or recipient peak transaminase levels was assessed. RESULTS: Among 23 livers, eight were considered unsuitable for transplantation, leaving 15 livers for assessment. Higher initial hemoglobin was associated with a lower risk of EAD (0% vs. 55.6%, p = 0.04). Perfusate hemoglobin decreased after NMP initiation (p = 0.003) and negatively correlated with recipient peak transaminase levels (ALT: ρ = -0.72, p = 0.002; AST: ρ = -0.79, p < 0.001). Consistently, higher hemoglobin livers also demonstrated lower perfusate liver enzymes. CONCLUSIONS: Perfusate hemoglobin levels decreased during NMP, and lower perfusate hemoglobin levels were associated with a higher incidence of EAD and higher levels of liver injury markers. Maintaining higher hemoglobin levels during NMP may help reduce ischemia-reperfusion injury and prevent or attenuate EAD. Larger prospective studies are needed to validate the findings of this pilot study.

The Impact of Early Positive Studies on the Evolution of Extracorporeal Albumin Dialysis Literature: A Bibliometric Analysis.

INTRODUCTION: Liver failure is a life-threatening condition characterized by the accumulation of metabolic toxins. Extracorporeal albumin dialysis (ECAD) has been promoted as a possible therapy. METHODS: We employed bibliometric analysis to scrutinize the conceptual, intellectual, and social structure of the ECAD literature including its co-citation network and thematic analysis to explore its evolution and organization. RESULTS: We identified 784 documents with a mean of 30.25 citations per document in a corpus of 15,191 references. The average citation rate peaked in 1998 at 280.75 citations/year before a second 2013 peak of 54.81 citations/year and then progressively decreased to its nadir in 2022 (1.48 yearly citations). We identified four primary co-citation clusters, with the most impactful publications being small "positive" manuscripts by Mitzner et al. (2000) and Heemann et al. (2002) (Cluster 1). This first cluster had several relational citations with clusters 2 and 3, but almost no citation link with cluster 4 represented by Bañares et al. (2013), Saliba et al. (2013), and Larsen et al. (2016), with their three negative randomized controlled trials. Finally, the thematic map revealed a shift in focus over time, with inflammation and ammonia as recent emergent themes. CONCLUSIONS: This bibliometric analysis provided a transparent and reproducible longitudinal assessment of ECAD literature and demonstrated how positive studies with low levels of evidence can dominate a research field and overshadow negative findings from higher quality studies. These insights hold significant implications for future research and clinical practice within this domain.

Cardiac Output Changes during Renal Replacement Therapy: A Scoping Review.

INTRODUCTION: Renal replacement therapy (RRT) is associated with hypotension. However, its impact on cardiac output (CO) is less understood. We aimed to describe current knowledge of CO monitoring and changes during RRT. METHODS: We searched MEDLINE, Embase, and Cochrane from January 1, 2000, to January 31, 2023, using Covidence for studies of intermittent hemodialysis (IHD) and continuous RRT (CRRT) with at least three CO measurements during treatment. Two independent reviewers screened citations, and a third resolved disagreements. The findings did not allow meta-analysis and are presented descriptively. RESULTS: We screened 3,285 articles and included 48 (37 during IHD, nine during CRRT, and two during both). Non-invasive devices (electrical conductivity techniques and finger cuff pulse contour) were the most common CO measurement techniques (21 studies). The median baseline cardiac index in IHD studies was 3 L/min/m2 (95% CI, 2.7-3.39). Among the 88 patient cohorts studied, a decrease in CO occurred in 63 (72%). In 16 cohorts, the decrease was severe (>25%). Changes in blood pressure (BP) were not concordant in extent or direction with changes in CO. The decrease in CO correlated weakly with ultrafiltration rate (r = -0.3, p = 0.05) and strongly with changes in systemic vascular resistance (SVR) (r = -0.6, p < 0.001). CONCLUSION: There are limited data on CO changes during RRT. However, a decrease in CO appeared common and was marked in 1 of 5 patient cohorts. Such decreases often occurred without BP changes and were associated with increased SVR.

Relative Blood Volume Monitoring during Continuous Renal Replacement Therapy: A Prospective Observational Study.

INTRODUCTION: Hematocrit monitoring during continuous renal replacement therapy (CRRT) allows the continuous estimation of relative blood volume (RBV). This may enable early detection of intravascular volume depletion prior to clinical sequelae. We aimed to investigate the feasibility of extended RBV monitoring and its epidemiology during usual CRRT management by clinicians unaware of RBV. Moreover, we studied the association between changes in RBV and net ultrafiltration (NUF) rates. METHODS: In a cohort of adult intensive care unit patients receiving CRRT, we continuously monitored hematocrit and RBV using a pre-filter noninvasive optical sensor. We analyzed temporal changes in RBV and investigated the association between RBV change and NUF rates, using the classification of NUF rates into low, moderate, or high based on predefined cut-offs. RESULTS: We obtained >60,000 minute-by-minute measurements in >1,000 CRRT hours in 36 patients. The median RBV change was negative (decrease) in 69% of patients and the median peak change in RBV was -9.3% (interquartile range: -3.9% to -14.3%). Moreover, the median RBV decreased from baseline by >5% in 40.2% of measurements and by >10% in 20.6% of measurements. Finally, RBV decreased significantly more when patients received a high NUF rate (>1.75 mL/kg/h) compared to low or moderate NUF rates (5.32% vs. 1.93% or 1.97%, p < 0.001). CONCLUSION: Continuous hematocrit and RBV monitoring during CRRT was feasible. RBV decreased significantly during CRRT, and decreases were greater with higher NUF rates. RBV monitoring may help optimize NUF management and prevent the occurrence of intravascular volume depletion.

A Pilot and Feasibility Study of Continuous Cardiac Output and Blood Pressure Monitoring during Intermittent Hemodialysis.

INTRODUCTION: Hypotension is common during intermittent hemodialysis (IHD) and may be due to a decreased cardiac index (CI). However, no study has simultaneously and continuously measured CI and mean arterial pressure (MAP) to understand the prevalence, severity, and duration of CI decreases or relate them to MAP, blood volume (BV), and net ultrafiltration (NUF) rate. METHODS: In a prospective, pilot and feasibility investigation, we studied 10 chronic IHD patients. We used the ClearSight System™ to continuously monitor CI and MAP; the CRIT-LINE®IV monitor to detect BV changes and collected data on NUF rate. RESULTS: Device tolerance and compliance were 100%. All patients experienced at least ≥1 episode of severe CI decrease (>25% from baseline), with a median duration of 24 min (IQR 6-87) and of 68 min [14-106] for moderate decreases (>15% but ≤25% from baseline). Eight patients experienced a low CI state (<2.2 L/min/m2). The lowest CI was 0.9 L/min/m2 with a concomitant MAP of 94 mm Hg. When the fall in CI was severe, MAP increased in 58% of cases and remained stable in 28%. Overall, CI decreased by -0.55 L/min/m2 when BV decrease was moderate versus mild (p < 0.001) and by -0.8 L/min/m2 when NUF rate was high versus low (p < 0.001). CONCLUSION: Continuous CI monitoring is feasible in IHD and shows frequent moderate-severe CI decreases, sometimes to low CI state levels. Such decreases are typically associated with markers of decreased intravascular volume status but not with a decrease in MAP, implying marked vasoconstriction.

Carboxyhemoglobin as Potential Biomarker for Cardiac Surgery Associated Acute Kidney Injury.

OBJECTIVES: Carboxyhemoglobin (CO-Hb) is a marker of hemolysis and inflammation, both risk factors for cardiac surgery-associated AKI (CSA-AKI). However, the association between CO-Hb and CSA-AKI remains unknown. DESIGN: A retrospective cohort study. SETTING: Tertiary university-affiliated metropolitan hospital: single center. PARTICIPANTS: Adult on-pump cardiac surgery patients from July 2014 to June 2022 (N = 1,698). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were stratified into quartiles based on CO-Hb levels at intensive care unit (ICU) admission. A progressive increased risk of CSA-AKI was observed with higher CO-Hb levels at ICU admission. On multivariable logistic regression analysis, the highest quartile (CO-Hb ≥ 1.4%) showed an independent association with the occurrence of CSA-AKI (odds ratio 1.45 compared to the lowest quartile [CO-Hb < 1.0%], 95% CI 1.023-2.071; p = 0.038). Compared to patients with CO-Hb <1.4%, patients with CO-Hb ≥ 1.4% at ICU admission had significantly higher postoperative creatinine (135 vs 116 µmol/L, p < 0.001), higher rates of postoperative RRT (6.7% vs 2.3%, p < 0.001) and AKI (p < 0.001) on univariable analysis and shorter time to event for AKI or death (p < 0.001). CONCLUSIONS: CO-Hb ≥ 1.4% at ICU admission is an independent risk factor for CSA-AKI, which is easily obtainable and available on routine arterial blood gas measurements. Thus, CO-Hb may serve as a practical and biologically logical biomarker for risk stratification and population enrichment in trials of CSA-AKI prevention.

Renal medullary oxygenation during laparoscopic vs open surgery: the impact of blood pressure management-a pilot randomized controlled trial.

The impact of blood pressure targets and surgical approach (laparoscopic or open) on continuous urinary oxygenation (PuO2), a validated surrogate of renal medullary PO2, during general surgery, is unclear. We aimed to assess the effects of different blood pressure targets and surgical procedures on PuO2. We randomized patients receiving either laparoscopic or open surgery into two mean arterial pressure (MAP) target groups: usual MAP or a high MAP. We measured PuO2 in real-time and analyzed it according to the type of surgery and blood pressure target. The study was retrospectively registered on the 5th of July 2023 (ACTRN12623000726651). We included 43 participants who underwent either laparoscopic (n = 20) or open surgery (n = 23). We found that PuO2 significantly decreased during both laparoscopic and open surgery under a usual blood pressure target (- 51% and - 49%, respectively). However, there was a sharper fall with laparoscopic surgery resulting in a higher PuO2 with open surgery (mean difference: 11 ± 1 mmHg higher; p < 0.001). Targeting a higher MAP resulted in a higher PuO2 over time during laparoscopic surgery (mean difference: 7 ± 1 mmHg, p < 0.001). In contrast, targeting a usual MAP resulted in a higher PuO2 during open surgery (mean difference: 7 ± 1 mmHg, p < 0.001). Surgical approach and intraoperative blood pressure targets significantly impact urinary oxygenation. Further studies with larger sample sizes are needed to confirm these findings and understand their potential clinical implications.Registration number: ACTRN12623000726651; Date of registration: 05/07/2023 (retrospectively registered).

Complications associated with prone positioning in mechanically ventilated COVID-19 patients: A multicentre, retrospective observational study.

BACKGROUND AND AIMS: Prone positioning is commonly applied to improve gas exchange in mechanically ventilated patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Whilst prone positioning is effective, specific complications may arise. We aimed to assess the prevalence of specific complications related to prone positioning in patients mechanically ventilated for COVID-19-related ARDS. DESIGN: Multicentre, retrospective observational study. METHODS: Multi-centre observational study of mechanically ventilated patients with COVID-19-related ARDS admitted to intensive care units in Melbourne, Australia, from August to November 2021. Data on baseline characteristics, prone positioning, complications, and patient outcomes were collected. RESULTS: We assessed 553 prone episodes in 220 patients across seven sites (mean ± standard deviation age: 54 ± 13 years, 61% male). Overall, 58% (127/220) of patients experienced at least one prone-positioning-related complication. Pressure injury was the most prevalent (n = 92/220, 42%) complication reported. Factors associated with increased risk of pressure injury were male sex (adjusted odds ratio = 1.15, 95% confidence interval: [1.02-1.31]) and the total number of prone episodes (adjusted odds ratio = 1.11, 95% confidence interval: [1.07-1.15]). Device dislodgement was the next most common complication, occurring in 28 of 220 (13%) patients. There were no nerve or retinal injuries reported. CONCLUSIONS: Pressure injuries and line dislodgement were the most prevalent complications associated with prone positioning of patients mechanically ventilated for COVID-19. The risk of pressure injuries was associated with male sex and the number of prone positioning episodes.

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.

Exploring the norepinephrine to angiotensin II conversion ratio in patients with vasodilatory hypotension: A post-hoc analysis of the ARAMIS trial.

PURPOSE: Angiotensin II is approved for catecholamine-refractory vasodilatory shock but the conversion dose ratio from norepinephrine to angiotensin II remains unclear. METHODS: We conducted a post-hoc analysis of the Acute Renal effects of Angiotensin II Management in Shock (ARAMIS) trial involving patients with vasodilatory hypotension. We determined the norepinephrine equivalent dose immediately prior to angiotensin II initiation and calculated the conversion dose ratio between norepinephrine and angiotensin II. We performed subgroup analyses based on recent exposure to angiotensin receptor blockers (ARBs) and renin levels at baseline. RESULTS: In 37 patients, the median conversion dose ratio between norepinephrine equivalent and angiotensin II was to 10:1 for norepinephrine bitartrate (5:1 for norepinephrine base). The conversion ratio was not affected by the baseline renin, with a median ratio of 10 (7-21) in the high renin group versus 12 (5-22) in the low renin group. Finally, exposure to ARBs prior admission appeared to diminish the conversion ratio with a median ratio of 7 (4-13) in ARB patients vs. 12 (7-22) in non-ARB patients. CONCLUSIONS: The norepinephrine to angiotensin II conversion dose ratio is 10:1 in a vasodilatory hypotension population. These findings can guide clinicians and researchers in the use, dosing, and study of angiotensin II in critical care.

Methemoglobin in critically ill septic patients.

Aim: Higher nitric oxide (NO) levels correlate with adverse sepsis outcomes but are challenging to measure. Methemoglobin (MetHb), a measurable product of NO, has not been utilized for risk stratification.Methodology: All patients with sepsis admitted to the intensive care unit (ICU) that had at least one MetHb measurement within 24 h of ICU admission were retrospectively analyzed. We assessed the epidemiology and associations of MetHb with hospital mortality.Results: Among 7724 patients, 1046 qualified. Those with MetHb ≥1.6% showed significantly higher mortality and fewer days alive outside the hospital by day 28. MetHb levels ≥1.6% independently predicted increased 28-day mortality.Conclusion: Our findings suggest MetHb, easily obtainable from arterial blood gases, can significantly enhance sepsis risk stratification.

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Intraoperative dexamethasone is associated with a lower risk of respiratory failure in thoracic surgery: Observational cohort study (SURTHODEX).

BACKGROUND: Postoperative complications, particularly respiratory complications, are of significant clinical concern in patients undergoing elective thoracic surgery. Dexamethasone (DXM), commonly administered to prevent postoperative nausea and vomiting (PONV), has potential anti-inflammatory effects that might be beneficial in reducing these complications. We aimed to investigate whether intraoperative DXM administration could mitigate the occurrence of respiratory complications following elective thoracic surgery. METHODS: We conducted a single-center observational study, including patients who underwent elective thoracic surgery from 2012 to 2020. The primary outcome was the onset of acute respiratory failure within 7 days post-surgery. Secondary outcomes encompassed other postoperative complications, duration of hospital stay, and mortality within 30 days post-surgery. An overlap propensity score analysis was employed to estimate the treatment effect. RESULTS: We included 1,247 adult patients, 897 who received dexamethasone (DXM) and 350 who served as controls. Intraoperative dexamethasone administration was associated with a significant reduction in respiratory complications with an adjusted relative risk (RR) of 0.65 (95% CI: 0.43-0.97). There was also a significant decline in composite infectious criteria with an adjusted RR of 0.76 (95% CI: 0.63-0.93). Cardiac complications were also assessed as a composite criterion, and a significant reduction was observed (adjusted RR, 0.68; 95% CI, 0.51-0.9). However, there were no association with mechanical complications, mortality within 30 days (adjusted RR of 0.43, 95% CI: 0.17-1.09) or in the length of hospital stay (adjusted RR of 0.85, 95% CI: 0.71-1.02). CONCLUSIONS: Dexamethasone administration was associated with a reduction in postoperative respiratory complications. Further prospective studies are needed to confirm these findings.

Rapid uptake of adjunctive corticosteroids for critically ill adults with septic shock following publication of ADRENAL trial. A multicenter, retrospective analysis of prescribing practices in Queensland Intensive Care Units.

BACKGROUND: Septic shock is common and associated with significant morbidity and mortality. The ADRENAL trial examined the use of hydrocortisone in patients with septic shock, demonstrating no difference in patient-centred outcomes but a decrease in the time to shock resolution. The change in clinical practice related to the publication of the ADRENAL trial is currently unknown. METHODS: A retrospective cohort study examining the use of hydrocortisone in patients with septic shock was conducted in 12 intensive care units (ICUs). A segmented linear regression was performed to identify a stepwise change in hydrocortisone administration and 90-day mortality associated with the publication of the ADRENAL trial. RESULTS: We included 4,198 patients with a mean age of 58 years (standard deviation, SD17), and the median noradrenaline equivalent score (NEE) was 0.07 µg/kg/min (IQR 0.02 - 0.17). Segmented regression analysis for hydrocortisone administration identified two breakpoints, 3 months before and 6 months after publication, leading to three periods: Pre-publication, Transition and Post-publication. Compared to the pre-publication period, the Transition and Post-publication cohorts had a higher proportion of hydrocortisone administration (28% vs. 34% vs. 43%; p < 0.0001). Furthermore, after adjustment for temporal change, the transition period had a significant change in the slope of the proportion of patients receiving hydrocortisone (-0.1% per month vs. +1.4% per month; p = 0.026), whereas this was not statistically significant during the post-publication period (+0.1% per month, p = 0.66). After adjusting for confounders, the Transition and Post-publication periods were independently associated with an increase in hydrocortisone (OR 1.4, 95% CI 1.14 - 1.77; p = 0.0015 and OR 2.03; 95% CI 1.74 - 2.36; p < 0.001, respectively). Furthermore, after adjusting for confounders, when compared to the Pre-transition period, the use of hydrocortisone was associated with a statistically significant decrease in 90-day mortality (14% vs. 24% absolute difference, aHR for hydrocortisone effect -0.81; 95% CI 0.65 - 0.99; p = 0.044). CONCLUSION: Publication of the ADRENAL trial changed clinical practice in Queensland ICUs with increased prescription of hydrocortisone for patients with septic shock with an associated reduction in mortality.

Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.

PURPOSE: Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. METHODS: Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. RESULTS: We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). CONCLUSION: During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.

Clinical Warburg effect in lymphoma patients admitted to intensive care unit.

BACKGROUND: The Warburg effect, characterized by elevated lactate levels without tissue hypoxia or shock, has been described in patients with aggressive lymphoproliferative malignancies. However, the clinical characteristics and long-term outcomes in this population remain poorly understood. METHODS: We retrospectively analyzed 135 patients with aggressive lymphoproliferative malignancies admitted to the ICU between January 2017 and December 2022. Patients were classified into three groups: Clinical Warburg Effect (CWE), No Warburg with High Lactate level (NW-HL), and No Warburg with Normal Lactate level (NW-NL). Clinical characteristics and outcomes were compared between the groups and factors associated with 1-year mortality and CWE were identified using multivariable analyses. RESULTS: Of the 135 patients, 46 (34%) had a CWE. This group had a higher proportion of Burkitt and T cell lymphomas, greater tumor burden, and more frequent bone and cerebral involvement than the other groups. At 1 year, 72 patients (53%) died, with significantly higher mortality in the CWE and NW-HL groups (70% each) than in the NW-NL group (38%). Factors independently associated with 1-year mortality were age [HR = 1.02 CI 95% (1.00-1.04)], total SOFA score at admission [HR = 1.19 CI 95% (1.12-1.25)], and CWE [HR = 3.87 CI 95% (2.13-7.02)]. The main factors associated with the CWE were tumor lysis syndrome [OR = 2.84 CI 95% (1.14-7.42)], bone involvement of the underlying malignancy [OR = 3.58 CI 95% (1.02-12.91)], the total SOFA score at admission [OR = 0.81 CI 95% (0.69-0.91)] and hypoglycemia at admission [OR = 14.90 CI 95% (5.42-47.18)]. CONCLUSION: CWE is associated with a higher tumor burden and increased 1-year mortality compared to patients without this condition. Our findings underscore the importance of recognizing patients with CWE as a high-risk cohort, as their outcomes closely resemble those of individuals with lymphoma and shock, despite not requiring advanced organ support. Clinicians should recognize the urgency of managing these patients and consider early intervention to improve their prognosis.

Survival Benefit of Renin-Angiotensin System Blockers in Critically Ill Cancer Patients: A Retrospective Study.

Increasing evidence argues for the promotion of tumorigenesis through activation of the renin-angiotensin system pathway. Accordingly, a benefit of renin-angiotensin system blockers (RABs) treatments has been suggested in patients with solid cancers in terms of survival. We aimed to evaluate in-ICU survival and one-year survival in cancer patients admitted to the ICU with respect to the use of RABs. We conducted a retrospective observational single-center study in a 24-bed medical ICU. We included all solid cancer patients (age ≥ 18 years) requiring unplanned ICU admission. From 2007 to 2020, 1845 patients with solid malignancies were admitted (median age 67 years (59-75), males 61.7%). The most frequent primary tumor sites were the gastrointestinal tract (26.8%), the lung (24.7%), the urological tract (20.1%), and gynecologic and breast cancers (13.9%). RABs were used in 414 patients, distributed into 220 (53.1%) with angiotensin-receptor blockers (ARBs) and 194 (46.9%) with angiotensin-converting enzyme inhibitors (ACEis). After multivariate adjustment, ARBs use (OR = 0.62, 95%CI (0.40-0.92), p = 0.03) and ACEis use (OR = 0.52, 95%CI (0.32-0.82), p = 0.006) were both associated with improved in-ICU survival. Treatment with ARBs was independently associated with decreased one-year mortality (OR = 0.6, 95%CI (0.4-0.9), p = 0.02), whereas treatment with ACEis was not. In conclusion, this study argues for a beneficial impact of RABs use on the prognosis of critically ill cancer patients.