Ravindranath Tiruvoipati

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Background: The Sodium Bicarbonate for Metabolic Acidosis in the ICU (SODa-BIC) trial assessed the effect of sodium bicarbonate on Major Adverse Kidney Events at 30 days (MAKE30) in critically ill patients with metabolic acidosis. Although the trial demonstrated no significant difference in the primary outcome, the individual components showed differing magnitudes and directions of […] ABSTRACT Background: The Sodium Bicarbonate for Metabolic Acidosis in the ICU (SODa-BIC) trial assessed the effect of sodium bicarbonate on Major Adverse Kidney Events at 30 days (MAKE30) in critically ill patients with metabolic acidosis. Although the trial demonstrated no significant difference in the primary outcome, the individual components showed differing magnitudes and directions of […]

Severe acute respiratory distress syndrome (ARDS) is associated with substantial morbidity and mortality ranging from 37 to 44%. Although extracorporeal membrane oxygenation (ECMO) is often indicated in ARDS, it is an invasive and resource-intensive intervention and may be contraindicated when the anticipated survival benefit is low. We describe two patients with severe ARDS with multiorgan failure for whom ECMO could not be provided. The first patient was deemed ineligible for ECMO due to advanced multiorgan dysfunction. The second was considered suitable, but the family declined transfer to an ECMO-capable center. In both cases, low-flow extracorporeal carbon dioxide removal (ECCO ₂ R) was instituted as part of a multimodal strategy that included renal replacement therapy, prone-position ventilation, and inhaled nitric oxide. ECCO ₂ R facilitated effective control of hypercapnic acidemia and allowed lung-protective ventilation. Both patients fully recovered and were discharged home. These cases provide proof of concept for ECCO ₂ R as part of a multimodal strategy and suggest a potential role as an adjunctive therapy in selected patients when escalation of conventional ventilation is constrained by lung-protective limits, and ECMO is unavailable or contraindicated. These observations represent a descriptive feasibility experience and warrant further evaluation in resource-limited and clinically complex settings.

Background: Damage to the enteric nervous system in murine Clostridioides difficile infection (CDI) has recently been postulated as an explanation for the paradoxical dysmotility, including ileus, observed in a disease generally characterized by diarrheal onset. However, the clinical spectrum and mortality implications of acute gastrointestinal dysmotility remain under-explored in human CDI. Methods: We conducted the first retrospective cohort study of hospitalized adults (≥18 years) with CDI at a single tertiary health service in Australia between January 2018 and December 2021, defining clinical and radiologic features of gastrointestinal dysmotility at diagnosis, during admission, and in relation to the timing of diarrheal onset. Atypical presentations were defined as 1 or more CDI-associated symptoms persisting for >24 hours before diarrheal onset. Outcomes included time to diagnostic testing and directed therapy, 30- and 90-day mortality. Multivariable logistic and Cox regression models were used assessing independent risk factors associated with death. Results: Among 467 CDI episodes, dysmotility occurred in 32% at diagnosis and persisted radiologically for up to 6 weeks. Atypical presentations (91/467 [19.5%] episodes) were associated with significantly delayed treatment (median, IQR 4 [1–9] versus 2 [0–8] days, P < .001) and increased 90-day all-cause mortality compared with typical presentations (24.2% versus 9.6%, HR 2.62 [1.51–4.57], P = .001). Small-bowel involvement was identified in 44/270 (16.3%) baseline imaging episodes. Conclusions: Both large- and small-bowel dysmotility occur frequently in hospitalized adults with CDI, contributing to diagnostic delays and increased mortality among patients with atypical presentations. These findings support extension of global CDI guidance addressing diagnostic pathways and empiric therapy.

Background: Recent European Society of Clinical Microbiology and Infection and Australasian Society of Infectious Diseases Clostridioides difficile infection (CDI) management guidelines endorse the addition of intravenous tigecycline in patients who are progressing to fulminant infection. However, there are very limited data regarding clinical outcomes with this approach. Aims: We aimed to evaluate mortality and adverse outcomes after tigecycline combination therapy was commenced at the time of fulminant CDI. Methods: This retrospective single‐site observational study included patients between January 2018 and December 2022 treated with adjunctive intravenous tigecycline for fulminant CDI in addition to oral vancomycin and intravenous metronidazole. The primary outcome was all‐cause mortality at 30 days. Secondary outcomes included clinical cure, partial response, in‐hospital CDI‐attributable and 90‐day all‐cause mortality, colectomy and adverse events. Results: Eighteen patient episodes occurred, with median age 67.5 years, requiring intensive care admission and inotropic support in 66.7% and 50% of episodes respectively. All‐cause mortality at 30 days was 22.2%. Clinical cure occurred at 14 days in 16.7% of cases and partial response requiring further oral therapy in 55.6%. There was one colectomy and two serious adverse events, including a hyperkalaemic cardiac arrest in a haemodialysis patient and one significant intra‐abdominal bleeding episode requiring surgery. Conclusions: Tigecycline combination therapy resulted in improved all‐cause 30‐day mortality in high‐risk CDI patients versus historical data, without the use of faecal microbiota transplantation. Poor outcomes were seen in three patients with pre‐existing renal failure, and we question the efficacy and safety of tigecycline in this group. This is a useful salvage strategy, but monitoring for toxicity is essential.

Background: Low flow extracorporeal carbon dioxide removal (ECCO ₂ R) is used to assist in lung protective ventilation. The objective of this study was to compare the characteristics of patients who died in-hospital to those who survived and identify variables pre and during the first 24 h of ECCO ₂ R support independently associated with hospital mortality. Methods: This study is a multicenter, multinational, retrospective review of data from the Hemolung Registry between April 2013 and June 2021. The primary outcome was hospital mortality. Results: Of the 242 included patients 115 (48%) survived. Prior to ECCO ₂ R initiation and during the first 24 h of ECCO ₂ R therapy, patients who died had a lower PaO ₂ /FiO ₂ ratio but higher FiO ₂ , respiratory rate (RR), and tidal volumes. Age ((OR: 1.51 (95% CI: 1.06–2.14); p = 0.022), RR (1.92 (1.28–2.87); p = 0.002), and FiO ₂ (2.33 (1.50–3.62); p < 0.001) were independently associated with increased risk of mortality. Conclusions: Age, respiratory rate, and FiO ₂ during the first 24 h of ECCO ₂ R therapy were independently associated with increased risk of hospital mortality. An ongoing high FiO ₂ (>0.7) and respiratory rate ⩾25 during the first 24 h is independently associated with higher risk of hospital mortality.

Introduction: Extracorporeal carbon dioxide removal (ECCO ₂ R) is a type of partial extracorporeal respiratory support with potential to reduce lung injury in patients with hypercapnic respiratory failure. We aimed to study the current practice and perceptions of ECCO ₂ R and the need for an ECCO ₂ R registry. Methods: A multinational survey was conducted among clinicians who have published clinical studies on ECCO ₂ R or have used ECCO ₂ R within the last 5 years in Europe, Asia, Oceania and the United States. Results: Seventy responses from 140 requests (response rate: 50%) were received from physicians across all targeted regions. ECCO ₂ R is reported to be used mainly for ARDS (46%) management, followed by asthma (18%) and COPD (15%). Eighty‐five percent of the participants reported low case volumes (0–10 cases per year). Variations in the practice of ECCO ₂ R were evident, including triggers for initiating ECCO ₂ R, devices used, access catheter type and size, targeted blood flow rates and monitoring of anticoagulation. The most common barriers to wider use of ECCO ₂ R included lack of evidence, followed by the device's costs and operational complexity. Eighty‐four percent (48/57) of the respondents thought an ECCO ₂ R registry would be useful, and 98% (47/48) of the respondents reported that they would be willing to contribute to a dedicated ECCO ₂ R registry. Conclusion: ECCO ₂ R practices varied considerably, but most respondents agreed on the usefulness of a dedicated ECCO ₂ R registry. Practice variations may be associated with suboptimal outcomes. ECCO ₂ R quality indicators are needed to optimise clinical outcomes and resource utilisation.

OBJECTIVES: The mortality among patients admitted with sepsis remains high and varies depending on the site of infection. The impact of hypercapnia and acidemia on clinical outcomes in mechanically ventilated patients with sepsis is not well understood. DESIGN: Multicenter, binational, retrospective study assessed the association of compensated hypercapnia, hypercapnic acidemia, and nonrespiratory acidemia, in mechanically ventilated patients with mortality in sepsis. SETTING: Data were extracted from the “Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient” database over a 17-year period (from January 2006 to December 2022) from 201 ICUs. PATIENTS: Patients were classified into four mutually exclusive groups based on a combination of arterial pH and arterial C o ₂ recorded during the first 24 hours of ICU stay: normocapnia with normal pH, fully compensated hypercapnia, hypercapnic acidemia, and nonrespiratory acidemia. Logistic regression and Cox proportional hazards regression were used to examine the association of compensated hypercapnia, hypercapnic, and nonrespiratory academia to hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-two thousand four hundred five patients were included. Overall compensated hypercapnia (odds ratio [OR], 1.39; 95% CI, 1.24–1.55; p < 0.001), hypercapnic acidemia (OR, 1.68; 95% CI, 1.57–1.80; p < 0.001), and nonrespiratory acidemia (OR, 1.75; 95% CI, 1.61–1.90; p < 0.001) was associated with increased risk of hospital mortality as compared with patients with normocapnia and normal pH. The risk of increased hospital mortality associated with hypercapnic and nonrespiratory acidemia persisted in all prespecified diagnostic subgroups when compared with patients who had normal pH and normocapnia. Compensated hypercapnia was associated with increased mortality risk in neurologic and unspecified subgroups of sepsis. CONCLUSIONS: Hypercapnic acidemia and nonrespiratory acidemia within the first 24 hours of ICU admission are associated with increased risk of hospital mortality in mechanically ventilated patients with sepsis. This association remains consistent in all diagnostic subgroups of sepsis.