This study aims to investigate the association between serum bicarbonate levels and short-term outcomes in patients with acute kidney injury (AKI), with a focus on 14-day mortality and AKI progression within a 14-day period.

We conducted a secondary analysis using data from the Electronic Alerts for Acute Kidney Injury Amelioration (ELAIA) study. Serum bicarbonate levels and their associated outcomes were collected for all participants. Cox regression analysis and smooth curve fitting methods were employed to achieve the research objectives.

A total of 5,835 patients with AKI were included in the study. After adjustment for confounding factors, patients with serum bicarbonate concentrations below 22 mmol/L had a higher risk of both 14-day mortality and AKI progression compared to those with levels between 22 and 26 mmol/L (hazard ratio [HR] 1.90; 95% confidence interval [CI], 1.51-1.83 for mortality and HR 1.45; 95% CI, 1.23-1.71 for AKI progression, respectively). In contrast, patients with bicarbonate concentrations above 26 mmol/L had a lower risk of 14-day mortality (HR 0.70; 95% CI, 0.53-0.94) and AKI progression (HR 0.90; 95% CI, 0.74-1.10). Subsequent exploratory subgroup analyses revealed no statistically significant interactions (all p-values for interaction > 0.05) between 14-day mortality and serum bicarbonate levels.

In this cohort of AKI patients, serum bicarbonate concentrations below 22 mmol/L were associated with increased risks of 14-day mortality and AKI progression, while concentrations above 26 mmol/L were linked to a reduced risk of 14-day mortality.

Sodium bicarbonate is commonly administered to treat metabolic acidosis in intensive care units (ICUs). There is limited evidence from randomized trials to support this practice, and observational studies show conflicting results. Our aim was to perform a target trial emulation evaluating the effect of bicarbonate therapy on mortality.

Retrospective cohort study using data from 12 Australian ICUs. Inclusion criteria were adults with pH < 7.3 and PCO2 ≤ 45 mmHg within the first three days. We excluded repeat admissions, toxicology, diabetic ketoacidosis, and pre-existing end-stage renal failure. The treatment intervention was sodium-bicarbonate administration, and the primary outcome was 30-day ICU mortality with ICU discharge as a competing event. We evaluated multiple subgroups, including patients with acute kidney injury, requirement for vasoactive therapy, and pH < 7.2. The primary model utilized a parametric g-computation and rolling entry matching was performed as a sensitivity analysis.

We identified 6157 eligible admissions, of which 1764 (29%) received sodium bicarbonate. Bicarbonate therapy was associated with a 1.9% absolute mortality reduction for the primary analysis [risk ratio 0.86, 95% confidence interval (CI) 0.80 to 0.91], and significant benefits were seen across all subgroups evaluated. A similar point estimate of 2.1% was observed in the sensitivity analysis, with a sustained mortality reduction seen at 30 days.

In this target trial emulation, bicarbonate administration was associated with a small but statistically significant reduction in mortality for patients with metabolic acidosis. Large sample sizes would be required to demonstrate this effect in a randomized trial.

In critically ill patients, acid-base disorders are common before start of continuous renal replacement therapy. The aim of this study was to determine the influence of a high bicarbonate replacement fluid (30 mmol/L, Phoxilium®) on underlying acid-base disturbances.

This single-center retrospective study included patients treated with continuous veno-venous hemofiltration (CVVH) at a medical ICU from January 2018 to May 2019. All patients received CVVH with regional citrate anticoagulation (RCA) and a high bicarbonate RF (Phoxilium®). Patients were categorized based on their initial pH. Acid-base parameters were closely monitored over 72 h at pre-specified intervals.

The study included 64 patients with a median age of 68 years. At the start of CVVH, 56.3% (n = 36) had acidemia, 12.5% (n = 8) had alkalemia and 32.3% (n = 20) had a normal pH. The median pH of patients with acidemia [0 h: 7.28 (interquartile range 7.23-7.33)] was corrected quickly to the normal range within 8 h [7.36 (interquartile range 7.29-7.4)]. The median pH of patients with alkalemia took longer (48 h) to reach normal values and patients with a normal pH showed a further pH increase within the normal range over the 72 h. All patients showed an increasing bicarbonate and base excess from 24 to 72 h.

The RF in CVVH with RCA appears to be one of several factors influencing acid-base balance. Patients with different pre-existing acid-base disorders showed distinct correction kinetics. Prospective studies are needed to determine the clinical relevance of these findings and to optimize RF composition for better patient outcomes.

The Sequential Organ Failure Assessment (SOFA) score originated as a tool for assessing organ dysfunction in critical illness but has expanded to become an outcome measure in clinical trials. We aimed to assess how the SOFA score was used as the primary or secondary endpoint of major randomized controlled trials (RCTs).

Independent reviewers searched MEDLINE/PubMed, Scopus, and Embase databases.

Articles were selected when they fulfilled: 1) RCT; 2) SOFA score was primary or secondary endpoint; and 3) published in the Lancet , New England Journal of Medicine , or Journal of the American Medical Association .

Data collection included study details, outcomes, statistical differences in SOFA score, choice of score statistics, timepoints of SOFA reporting, and how missing data and competing risks analysis were managed.

Twenty-three RCTs had SOFA score as outcome measure, eight used it as primary endpoint. Daily maximum SOFA was the key statistic in 11 RCTs, delta SOFA was used in eight, and mean SOFA in four. Mean SOFA was most frequently chosen as primary endpoint (4/8, 50%). There were 18 different outcome assessment timepoints, ranging from 1 to 28 days. Three RCTs reported statistically significant difference in SOFA between groups. Handling of missing SOFA scores was not described in ten of 23 RCTs. When described, it varied from study to study with variable imputation methods and variable accounting for the competing risk of mortality and ICU discharge.

There is major variability in the choice of summary statistic for SOFA score analysis and assessment timepoints, when using it as outcome measure in RCTs. There was either no information or great variability in the handling of missing values, use of imputation, and accounting for competing risk. The current use of SOFA scores in RCTs lacks sufficient reproducibility and statistical and methodological robustness.

Sepsis is a common condition associated with significant morbidity and mortality. Emergency physicians play a key role in the diagnosis and management of this condition.

This paper evaluates key evidence-based updates concerning the management of sepsis and septic shock for the emergency clinician.

Sepsis is a life-threatening syndrome, and rapid diagnosis and management are essential. Antimicrobials should be administered as soon as possible, as delays are associated with increased mortality. Resuscitation targets include mean arterial pressure ≥ 65 mmHg, mental status, capillary refill time, lactate, and urine output. Intravenous fluid resuscitation plays an integral role in those who are fluid responsive. Balanced crystalloids and normal saline are both reasonable options for resuscitation. Early vasopressors should be initiated in those who are not fluid-responsive. Norepinephrine is the recommended first-line vasopressor, and if hypotension persists, vasopressin should be considered, followed by epinephrine. Administration of vasopressors through a peripheral 20-gauge or larger intravenous line is safe and effective. Steroids such as hydrocortisone and fludrocortisone should be considered in those with refractory septic shock.

An understanding of the recent updates in the literature concerning sepsis and septic shock can assist emergency clinicians and improve the care of these patients.

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.

To assess the efficacy and safety of bicarbonate infusion in children with Acute Diarrhea and Severe Dehydration (ADSD) having severe Non-Anion Gap Metabolic Acidemia (sNAGMA).

Children (aged 1-144 mo) with ADSD and sNAGMA (pH ≤7.2 and/or serum bicarbonate ≤15 mEq/L) were enrolled in an open-label randomized design. Controls (n = 25) received WHO-recommended rehydration therapy with Ringer Lactate, while intervention group (n = 25) received additional bicarbonate deficit correction. Primary outcome was time taken to resolve metabolic acidemia (pH >7.30 and/or bicarbonate >15 mEq/L). Secondary outcome measures were adverse outcome [composite of pediatric intensive care unit (PICU) transfer and deaths], acute care area free days in 5 d (ACAFD5), hospital stay, and adverse effects.

Time taken to resolve metabolic acidemia was significantly lesser with intervention [median (IQR); 8 h (4, 12) vs. 12 h (8, 24); p = 0.0067]. Intervention led to acidemia resolution in significantly more children by 8 h and 16 h (17/25 vs. 9/25, p = 0.035 and 23/25 vs. 17/24, p = 0.018, respectively). Patients with fluid refractory shock needed lesser inotropes in intervention group [median Vasoactive Inotrope Score (VIS), 10.5 vs. 34]. Intervention led to significantly lesser adverse outcome (0/25 vs. 5/25, p = 0.049), and noticeably more ACAFD5 [median (IQR); 2 (1, 2) vs. 1 (1, 2); p = 0.12]. Two patients died in the control group while none in the intervention group. No adverse effect was documented.

Additional calculated dose of bicarbonate infusion led to significantly early resolution of metabolic acidemia, lesser utilization of critical care facilities, and lesser adverse outcome in children with ADSD and sNAGMA, compared to standard therapy, with no adverse effect.

The use of sodium bicarbonate for metabolic acidosis has been a topic of debate, primarily due to the lack of clinical efficacy evidence. This study aims to identify which types of patients with various acid-base balance parameters can benefit from sodium bicarbonate therapy.

Patients diagnosed with metabolic acidosis were screened from a large multi-center critical care database to form a retrospective cohort. Mortality curves, logistic regression analysis, simulation methods, and propensity scores were used to compare data between sodium bicarbonate (SOB group) and non-treated (Non-SOB group) patients.

There was an interaction between baseline chloride, anion gap levels and sodium bicarbonate therapy on patients' in-hospital death. As chloride levels increased, the in-hospital mortality curves of the SOB group and Non-SOB group gradually converged, with the difference narrowing from approximately 20 % to 10 %, and then gradually widened with the increase of the anion gap. Furthermore, when patients had high chloride levels (≥112 mmol/L), those in the SOB group exhibited a higher incidence of hypernatremia, hypokalemia, and hypocalcemia at 24 h, and a lower incidence of hyperchloremia. Patients in SOB group also had a lower simulated mortality. Among patients treated with sodium bicarbonate, those with low chloride had more difficulty in normalizing pH compared to those with high chloride.

This study identified an interaction between baseline chloride and sodium bicarbonate therapy on patient survival. Hyperchloremic metabolic acidosis may potentially benefit from sodium bicarbonate therapy. Further prospective randomized controlled studies are warranted.

Clinical trials focusing on critically ill patients with metabolic acidosis, a common exclusion criterion is the presence of a PaCO2 > 45 mmHg. The aim of this study was to assess the impact of mild hypercapnia on patient characteristics, severity, and clinical outcomes in critically ill patients with metabolic acidosis.

Multicentre, retrospective, observational study conducted in 12 intensive care units (ICUs) in Queensland, Australia. Patients with metabolic acidosis and concurrent vasopressor requirement were included and the exposure of interest was the PaCO2 level at the time of meeting the eligibility criteria divided in two groups: PaCO2 ≤ 45 mmHg and PaCO2 46-50 mmHg. Primary clinical outcome was major adverse kidney events within 30 days (MAKE30).

We studied 5601 patients, with 3605 (64.4 %) in the PaCO2 ≤ 45 mmHg group and 1996 (35.6 %) in the PaCO2 46-50 mmHg group. The incidence of MAKE30 was lower in the PaCO2 46-50 mmHg group (29 % vs. 34 %; OR, 0.79 [95 %CI, 0.69 to 0.90]; p < 0.001) as was the use of renal replacement therapy, and the incidence of acute kidney injury. After adjustment for confounders, no outcome was different between the groups. The maximum fall of pH associated with an increase of 1 mmHg of PaCO2 in the PaCO2 46-50 mmHg group was 0.006.

In patients with metabolic acidosis, after adjustment for potential confounders, mild hypercapnia does not increase the MAKE-30 rate and does not have a major impact on pH.

Septic shock is a significant challenge in the management of patients with burns and traumatic injuries when complicated by infection, necessitating prompt and effective haemodynamic support. This review provides a comprehensive overview of current strategies for vasopressor and fluid management in septic shock, with the aim to optimize patient outcomes. With regard to vasopressor management, we elaborate on the pharmacologic profiles and clinical applications of catecholamines, vasopressin derivatives, angiotensin II, and other vasoactive agents. Noradrenaline remains central to septic shock management. The addition of vasopressin, when sequentially added to noradrenaline, offers a non-catecholaminergic vasoactive effect with some clinical benefits and risks of adverse effects. Emerging agents such as angiotensin II and hydroxocobalamin are highlighted for their roles in catecholamine-resistant vasodilatory shock. Next, for fluid management, crystalloids are currently preferred for initial resuscitation, with balanced crystalloids showing benefits over saline. The application of albumin in septic shock warrants further research. High-quality evidence does not support large-volume fluid resuscitation, and an individualized strategy based on haemodynamic parameters, including lactate clearance and capillary refill time, is recommended. The existing knowledge suggests that early vasopressor initiation, particularly noradrenaline, may be critical in cases where fluid resuscitation takes inadequate effect. Management of refractory septic shock remains challenging, with novel agents like angiotensin II and methylene blue showing potential in recent studies. In conclusion, Further research is needed to optimize haemodynamic management of septic shock, particularly in developing novel vasopressor usage and fluid management approaches.

Perioperative metabolic acidosis negatively affects patient outcomes. Perioperative fluid therapy has a clinically significant effect on acid-base balance. This study was conducted to evaluate the effects of isotonic sodium bicarbonate infusion (ISB) versus balanced crystalloid solution (BCS) on perioperative acid-base balance, in terms of postoperative base excess, among patients undergoing emergency laparotomy for perforation peritonitis.

This prospective, randomized, single-center, double-blinded study was conducted in a tertiary hospital from October 2021 to November 2022. A total of 90 patients undergoing emergency laparotomy for perforation peritonitis were randomly assigned to receive either isotonic sodium bicarbonate (ISB) or Ringer's Lactate as a balanced crystalloid solution (BCS) for perioperative maintenance fluid therapy. The primary outcome was to compare the base excess (BE) at the end of surgery. The secondary outcomes were to compare the postoperative clinical outcomes, including the requirement of vasopressors, duration of mechanical ventilation, HDU/ICU stay, the incidence of AKI within seven days, the incidence of re-exploration, and in-hospital mortality. Additionally, pH, PaCO2, HCO3, BE, and lactates intraoperatively and up to 24 h postoperatively were also compared.

The median base excess (BE) values at the end of surgery were significantly better in the ISB group - 4.80 [- 6.80, - 4.10] as compared to the BCS group - 7.30 [- 8.50, - 6.30]. The ISB group had a lower incidence of postoperative AKI (9% ISB versus 24% BCS) and requirement of vasopressors (18% ISB versus 44% BCS). However, there was no major difference between the incidence of re-exploration, length of ICU/HDU stay, and in-hospital mortality.

Infusing isotonic sodium bicarbonate (ISB) for intraoperative maintenance fluid therapy in patients undergoing emergency laparotomy for perforation peritonitis significantly improves perioperative acid-base balance with better postoperative clinical outcomes compared to a balanced crystalloid solution (BCS).

Eligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings.

To summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine.

A systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor (The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate.

In total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria.

Most exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.

Sodium bicarbonate has been used in the treatment of different pathologies, such as hyperkalemia, cardiac arrest, tricyclic antidepressant toxicity, aspirin toxicity, acute acidosis, lactic acidosis, diabetic ketoacidosis, rhabdomyolysis, and adrenergic receptors' resistance to catecholamine in patients with shock. An ongoing debate about bicarbonate's efficacy and potential harm has been raised for decades because of the lack of evidence supporting its potential efficacy. Despite the guidelines' restrictions, sodium bicarbonate has been overused in clinical practice. The overuse of sodium bicarbonate could be because of the desire to correct the arterial blood gas parameters rapidly instead of achieving homeostasis by treating the cause of the metabolic acidosis. Moreover, it is believed that sodium bicarbonate may reverse acidosis-induced myocardial depression, hemodynamic instability, ventricular arrhythmias, impaired cellular energy production, resistance to catecholamines, altered metabolism, enzyme suppression, immune dysfunction, and ineffective oxygen delivery. On the other hand, it is crucial to pay attention to the potential harm that could be caused by excessive sodium bicarbonate administration. Sodium bicarbonate may cause paradoxical respiratory acidosis, intracellular acidosis, hypokalemia, hypocalcemia, alkalosis, impaired oxygen delivery, cerebrospinal fluid acidosis, and neurologic dysfunction. In this review, we discuss the pathophysiology of sodium bicarbonate-induced adverse effects and potential benefits. We also review the most recent clinical trials, observational studies, and guidelines discussing the use of sodium bicarbonate in different pathologies.

Electrolyte disturbances are prevalent complications in critically ill patients with sepsis, significantly impacting patient prognosis. However, the specific association between serum potassium levels and mortality risk in this population remains poorly understood. This study aimed to investigate the association between serum potassium levels during hospitalization and the risk of 28-day and 90-day mortality in critically ill patients with sepsis.

Data were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV) database, and patients with severe sepsis requiring ICU admission were stratified into quartiles based on their mean serum potassium levels. Outcomes assessed included 28-day and 90-day mortality. A multivariate Cox proportional hazards model was used to investigate the association between serum potassium levels and mortality, with restricted cubic splines to identify potential nonlinear correlations. A dichotomous Cox proportional hazards model was applied to analyze the association further, and Kaplan-Meier analysis assessed the mortality risk across different potassium ranges.

A total of 25,203 patients were included, with 28-day and 90-day mortality rates of 27.84% and 40.48%, respectively. Multivariate analysis showed a significant association between serum potassium levels and mortality. Restricted cubic splines identified an inflection point at 4.4 mmol/L, with potassium levels above this threshold associated with higher mortality (28-day mortality: HR 2.96, 95% CI = 2.43-3.60; 90-day mortality: HR 2.19, 95% CI = 1.81-2.64). Kaplan-Meier analysis confirmed a significantly higher risk of death for patients with serum potassium levels above 4.4 mmol/L compared to those within the 3.5-4.4 mmol/L range (P<0.001).

In critically ill patients with sepsis, serum potassium levels exceeding 4.4 mmol/L are associated with an increased risk of death. Maintaining the average serum potassium level within the range of 3.5-4.4 mmol/L appears to be safe and may contribute to better outcomes in this patient population.

Sepsis is defined as "being evoked as a life-threatening organ dysfunction caused by an inadequate host response to infection". The most recent German S3 guidelines were published in 2018 and the Surviving Sepsis Campaign (SSC) last published the current recommendations for the treatment of sepsis and septic shock in 2021.

This article explores and discusses which evidence in the treatment of sepsis and septic shock has been confirmed.

Discussion of the 2018 German S3 guidelines, supplementation of the content of the 2021 international guidelines and recent research results since 2021.

The primary objective for managing sepsis and septic shock still includes rapid identification, early initiation of anti-infective treatment, and focus cleansing when feasible. In addition, the focus is on hemodynamic stabilization, including the early use of vasopressors for prevention of hypervolemia and, if necessary, the use of organ support procedures. Supportive treatment, such as the administration of corticosteroids and the use of apheresis, can be advantageous in specific scenarios. The focus is increasingly shifting towards post-intensive care unit (ICU) follow-up care, improving the quality of life after surviving sepsis and the close involvement of relatives of the patient.

Despite the fact that considerable progress has been made in understanding the pathophysiology and treatment of sepsis, the early administration of anti-infective agents, focus control, nuanced volume therapy and the use of catecholamines continue to be fundamental to sepsis management. New recommendations emphasize the early use of vasopressors (primarily norepinephrine) and the administration of corticosteroids, especially in cases of septic shock and pneumonia.

Cardiovascular disease (CVD) is responsible for approximately 30% of annual global mortality rates, yet existing treatments for this condition are considered less than ideal. Despite being previously overlooked, lactate, a byproduct of glycolysis, is now acknowledged for its crucial role in the cellular functions of the cardiovascular system. Recent studies have shown that lactate influences the proliferation, differentiation, and activation of immune cells through its modulation of post-translational protein modifications, thereby affecting the development and prognosis of cardiovascular disease. Consequently, there has been a notable increase in interest towards drug targets targeting lactylation in immune cells, prompting further exploration. In light of the swift advancements in this domain, this review article is dedicated to examining lactylation in cardiovascular disease and potential drug targets for regulating lactylation, with the aim of enhancing comprehension of this intricate field.

Acute kidney injury (AKI) is associated with increased mortality in critically ill patients. Due to differences in the etiology and pathophysiological mechanism, the current AKI criteria put it an embarrassment to evaluate clinical therapy and prognosis.

We aimed to identify subphenotypes based on routinely collected clinical data to expose the unique pathophysiologic patterns.

A retrospective study was conducted based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD), and a deep clustering approach was conducted to derive subphenotypes. We conducted further analysis to uncover the underlying clinical patterns and interpret the subphenotype derivation.

We studied 14,189 and 19,382 patients with AKI within 48 h of ICU admission in the two datasets, respectively. Through our approach, we identified seven distinct AKI subphenotypes with mortality heterogeneity in each cohort. These subphenotypes displayed significant variations in demographics, comorbidities, levels of laboratory measurements, and survival patterns. Notably, the subphenotypes could not be effectively characterized using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria alone. Therefore, we uncovered the unique underlying characteristics of each subphenotype through model-based interpretation. To assess the usability of the subphenotypes, we conducted an evaluation, which yielded a micro-Area Under the Receiver Operating Characteristic (AUROC) of 0.81 in the single-center cohort and 0.83 in the multi-center cohort within 48-hour of admission.

We derived highly characteristic, interpretable, and usable AKI subphenotypes that exhibited superior prognostic values.

Many dogmas influence daily clinical practice, and critical care medicine is no exception. We previously highlighted the weak, questionable, and often contrary evidence base underpinning four established medical managements-loop diuretics for acute heart failure, routine use of heparin thromboprophylaxis, rate of sodium correction for hyponatremia, and 'every hour counts' for treating bacterial meningitis. We now provide four further examples in this "Dogma II" piece (a week's course of antibiotics, diabetic ketoacidosis algorithms, sodium bicarbonate to improve ventricular contractility during severe metabolic acidosis, and phosphate replacement for hypophosphatemia) where routine practice warrants re-appraisal.

Patients presenting with or alerting emergency networks due to acute heart failure (AHF) form a diverse group with a plethora of symptoms, risks, comorbidities, and aetiologies. During AHF, there is an increased risk of destabilizing the functional substrate and modulatory adding to the risk of ventricular arrhythmias (VAs) already created by the structural substrate. New VAs during AHF have previously identified patients with higher intra-hospital and 60-day morbidity and mortality. Risk stratification and criteria/best time point for coronary intervention and implantable cardioverter defibrillator implantation, however, are still controversial topics in this difficult clinical setting. The characteristics and logistics of pre-hospital emergency medicine, as well as the density of centres capable of treating AHF and VAs, differ massively throughout Europe. Scientific guidelines provide clear recommendations for the management of arrhythmias in patients with chronic heart failure. However, the incidence, significance, and management of arrhythmias in patients with AHF have been less studied. This consensus paper aimed to address the identification and treatment of VAs that complicate the course of patients who have AHF, including cardiogenic shock.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can result in severe respiratory acidosis. Metabolic compensation is primarily achieved by renal retention of bicarbonate. The extent to which acute kidney injury (AKI) impairs the kidney's capacity to compensate for respiratory acidosis remains unclear.

This retrospective analysis covers clinical data between January 2009 and December 2021 for 498 ICU patients with AECOPD and need for respiratory support.

278 patients (55.8%) presented with or developed AKI. Patients with AKI exhibited higher 30-day-mortality rates (14.5% vs. 4.5% p = 0.001), longer duration of mechanical ventilation (median 90 h vs. 14 h; p = 0.001) and more severe hypercapnic acidosis (pH 7.23 vs. 7.28; pCO2 68.5 mmHg vs. 61.8 mmHg). Patients with higher AKI stages exhibited lower HCO3-/pCO2 ratios and did not reach expected HCO3- levels. In a mixed model analysis with random intercept per patient we analyzed the association of pCO2 (independent) and HCO3- (dependent variable). Lower estimates for averaged change in HCO3- were observed in patients with more severe AKI.

AKI leads to poor outcomes and compromises metabolic compensation of respiratory acidosis in ICU patients with AECOPD. While buffering agents may aid compensation for severe AKI, their use should be approached with caution.

Sepsis is a major cause of mortality worldwide and is the third-leading cause of death in the United States. Sepsis is resource-intensive and requires prompt recognition and treatment to reduce mortality. The impact of sepsis is not only on in-hospital survival but extends into post-discharge quality of life and risk of re-admission. As the understanding of sepsis physiology evolved, so have the recommended screening tools and treatment protocol which challenge prior standards of care. There have been noteworthy efforts by the Surviving Sepsis Campaign, the Third International Consensus Definitions for Sepsis and the Centers for Medicare and Medicaid Services to establish core measure bundles. This review highlights both the 2021 SSC International Guidelines and the 2015 CMS Severe Sepsis/Septic Shock Core Measure Bundle, or SEP-1. Notably, the SEP-1 bundle was implemented as a value-based purchasing program, linking care of sepsis patients to financial incentives. The objective is to explore the most current evidence-based data to inform clinical practice while utilizing the available guidelines as a roadmap.

Electrolyte disturbances are highly heterogeneous and severely affect the prognosis of critically ill patients. Our study was to determine whether data-driven phenotypes of seven electrolytes have prognostic relevance in critically ill patients.

We extracted patient information from three large independent public databases, and clustered the electrolyte distribution of ICU patients based on the extreme value, median value and coefficient of variation of electrolytes. Three plausible clinical phenotypes were calculated using K-means clustering algorithm as the basic clustering method. MIMIC-IV was considered a training set, and two others have been designated as verification set. The robustness of the model was then validated from different angles, providing dynamic and interactive visual charts for more detailed characterization of phenotypes.

15,340, 12,445 and 2147 ICU patients with electrolyte records during early ICU stay in MIMIC-IV, eICU-CRD and AmsterdamUMCdb were enrolled. After clustering, three reasonable and interpretable phenotypes are defined as α, β and γ according to the order of clusters. The α and γ phenotype, with significant differences in electrolyte distribution and clinical variables, higher 28-day mortality and longer length of ICU stay (p < 0.001), was further demonstrated by robustness analysis. The α phenotype has significant kidney injury, while the β phenotype has the best prognosis. In addition, the assignment methods of the three phenotypes were developed into a web-based tool for further verification and application.

Three different clinical phenotypes were identified that correlated with electrolyte distribution and clinical outcomes. Further validation and characterization of these phenotypes is warranted.

Sepsis manifests as a dysregulated immune response to an infection, leading to tissue damage, organ failure, and potentially death or long-term health issues. Sepsis remains a major health challenge globally, causing approximately 50 million cases and 11 million deaths annually. Early management of sepsis focuses on source control, antimicrobial treatment, and supporting vital organ function. Subsequent care includes metabolic, nutritional, and immune therapies to address the complex needs of septic patients. Metabolic management is based on obtaining moderate glucose targets. Nutritional support aims to mitigate hypercatabolism and muscle wasting, but aggressive early nutrition does not improve outcomes and could even be harmful. Immune modulation is crucial due to the dual nature of sepsis-induced immune responses. Corticosteroids have shown benefits in shock and organ dysfunction reversal and in mortality reduction with current guidelines recommending them in vasopressor therapy-dependent patients. In conclusion, sepsis management beyond the initial hours requires a multifaceted approach, focusing on metabolic, nutritional, and immune system support tailored to individual patient needs to enhance survival and recovery.

Vasopressor medications raise blood pressure through vasoconstriction and are essential in reversing the hypotension seen in many critically ill patients. Previously, vasopressor administration was largely limited to continuous infusions through central venous access.

This review addresses the clinical use of vasopressors in various shock states, including practical considerations and innovations in vasopressor administration. The focus is on the clinical administration of vasopressors across a range of shock states, including hypovolemic, distributive, cardiogenic, and obstructive shock.

Criteria for starting vasopressors are not clearly defined, though early use may be beneficial. A number of physiologic factors affect the body's response to vasopressors, such as acidosis and adrenal insufficiency. Peripheral and push-dose administration of vasopressors are becoming more common. Distributive shock is characterized by inappropriate vasodilation and vasopressors play a crucial role in maintaining adequate blood pressure. The use of vasopressors is more controversial in hypovolemic shock, as the preferred treatment is correction of the volume deficit. Evidence for vasopressors is limited in cardiogenic shock. For obstructive shock, vasopressors can temporize a patient's blood pressure until definitive therapy can reverse the underlying cause.

Across the categories of shock states, norepinephrine has wide applicability and is a reasonable first-line agent for shock of uncertain etiology. Keeping a broad differential when hypotension is refractory to vasopressors may help to identify adjunctive treatments in physiologic states that impair vasopressor effectiveness. Peripheral administration of vasopressors is safe and facilitates early administration, which may help to improve outcomes in some shock states.

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.

Acute kidney injury (AKI) is defined as an injury to the renal parenchyma, with or without a decrease in kidney function, as reflected by accumulation of uremic toxins or altered urine production (i.e., increased or decreased). AKI might result from any of several factors, including ischemia, inflammation, nephrotoxins, and infectious diseases. AKI can be community- or hospital-acquired. The latter was not previously considered a common cause for AKI in animals; however, recent evidence suggests that the prevalence of hospital-acquired AKI is increasing in veterinary medicine. This is likely due to a combination of increased recognition and awareness of AKI, as well as increased treatment intensity (e.g., ventilation and prolonged hospitalization) in some veterinary patients and increased management of geriatric veterinary patients with multiple comorbidities. Advancements in the management of AKI, including the increased availability of renal replacement therapies, have been made; however, the overall mortality of animals with AKI remains high. Despite the high prevalence of AKI and the high mortality rate, the body of evidence regarding the diagnosis and the management of AKI in veterinary medicine is very limited. Consequently, the International Renal Interest Society (IRIS) constructed a working group to provide guidelines for animals with AKI. Recommendations are based on the available literature and the clinical experience of the members of the working group and reflect consensus of opinion. Fifty statements were generated and were voted on in all aspects of AKI and explanatory text can be found either before or after each statement.

In the osteoporotic microenvironment, the acidic microenvironment generated by excessive osteoclasts not only causes irreversible bone mineral dissolution, but also promotes reactive oxygen species (ROS) production to induce osteoblast senescence and excessive receptor activator of nuclear factor kappa-B ligand (RANKL) production, which help to generate more osteoclasts. Hence, targeting the acidic microenvironment and RANKL production may break this vicious cycle to rescue osteoporosis. To achieve this, an acid-responsive and neutralizing system with high in vivo gene editing capacity is developed by loading sodium bicarbonate (NaHCO3) and RANKL-CRISPR/Cas9 (RC) plasmid in a metal-organic framework. This results showed ZIF8-NaHCO3@Cas9 (ZNC) effective neutralized acidic microenvironment and inhibited ROS production . Surprisingly, nanoparticles loaded with NaHCO3 and plasmids show higher transfection efficiency in the acidic environments as compared to the ones loaded with plasmid only. Finally, micro-CT proves complete reversal of bone volume in ovariectomized mice after ZNC injection into the bone remodeling site. Overall, the newly developed nanoparticles show strong effect in neutralizing the acidic microenvironment to achieve bone protection through promoting osteogenesis and inhibiting osteolysis in a bidirectional manner. This study provides new insights into the treatment of osteoporosis for biomedical and clinical therapies.

Acute kidney injury (AKI) is a complex and life-threatening condition with multifactorial etiologies, ranging from ischemic injury to nephrotoxic exposures. Management is founded on treating the underlying cause of AKI, but supportive care-via fluid management, vasopressor therapy, kidney replacement therapy (KRT), and more-is also crucial. Blood pressure targets are often higher in AKI, and these can be achieved with fluids and vasopressors, some of which may be more kidney-protective than others. Initiation of KRT is controversial, and studies have not consistently demonstrated any benefit to early start dialysis. There are no targeted pharmacotherapies for AKI itself, but some do exist for complications of AKI; additionally, medications become a key aspect of AKI management because changes in renal function and dialysis support can lead to issues with both toxicities and underdosing. This review will cover existing literature on these and other aspects of AKI treatment. Additionally, this review aims to identify gaps and challenges and to offer recommendations for future research and clinical practice.

Management of diabetic ketoacidosis (DKA) has internationally established guidelines. However, management of severe, refractory DKA with multiple contributors to acidosis, and management of DKA in patients with altered mentation, remain ambiguous. Use of sodium bicarbonate and intubation in DKA are unpopular treatment practices, but warrant consideration in these unique clinical scenarios. This paper describes a 61-year-old Sri Lankan female who presented with severe DKA, seizures and altered level of consciousness. In her case, the acidosis was secondary to DKA, hyperlactatemia, hyperchloraemic acidosis and acute kidney injury (AKI). Intravenous sodium bicarbonate was used in the management of acidosis. She was intubated due to altered level of consciousness with inadequate respiratory drive to compensate for metabolic acidosis. The outcome in her case was favorable. Intravenous sodium bicarbonate in DKA should be considered for patients with severe, refractory acidosis with hemodynamic instability, hyperkalemia and compounding acidosis due to normal anion gap acidosis or AKI. Intubation should be considered for patients with obtunded mentation unable to achieve respiratory compensation and obtunded mentation where reversal of DKA is unlikely to improve consciousness. Both strategies should be personalized with consideration of individual risk vs benefit.