Sodium Bicarbonate for Metabolic Acidosis in the ICU: Results of a Pilot Randomized Double-Blind Clinical Trial.

OBJECTIVES: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial. DESIGN: Investigator-initiated, parallel-group, pilot randomized double-blind trial. SETTING: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022. PATIENTS: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] < -4 mEq/L, and Pa co2 < 45 mm Hg). INTERVENTIONS: Sodium bicarbonate or placebo (5% dextrose). MEASUREMENTS AND MAIN RESULT: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-to-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference, -45.86 [95% CI, -63.11 to -28.61] hr; p < 0.001) and pH correction (median difference, -10.69 [95% CI, -19.16 to -2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI, -9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported. CONCLUSIONS: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Radiologically and clinically diagnosed acute pulmonary oedema in critically ill patients: prevalence, patient characteristics, treatments and outcomes.

Background: Acute pulmonary oedema is a life-threatening syndrome diagnosed based on radiological and clinical findings. However, to our knowledge, no studies have investigated this syndrome in critically ill patients. Objective: To describe the prevalence of radiologically and clinically diagnosed pulmonary oedema (RCDPO) in critically ill patients, characteristics of diagnosed patients, and treatments and outcomes in this patient population. Methods: We conducted a retrospective study using natural language processing to identify all radiological reports of pulmonary oedema among patients who had been admitted to single tertiary intensive care unit (ICU) over a 1-year period (January 2015 to January 2016). We reviewed clinical data, discharge diagnosis, treatment and outcomes for such patients, and used multivariable logistic regression analysis to identify the association of RCDPO with various outcomes. Results: Out of 2001 ICU patients, we identified 238 patients (11.9%) with RCDPO. Patients with RCDPO were more acutely ill, had more chronic liver disease and had more chronic renal failure than critically ill patients who did not have RCDPO. They were typically admitted with acute cardiovascular disease; were more likely to receive invasive mechanical ventilation and continuous renal replacement therapy; had longer duration of ICU and hospital stay; were more likely to die in hospital; and, if discharged alive, were more likely to be admitted to a chronic care facility. In total, 46 RCDPO patients (19.3%) died in hospital. On multivariable analysis, only age and continuous renal replacement therapy were independently associated with mortality. In contrast, invasive mechanical ventilation was associated with a 2.5 times greater odds of radiological resolution. Conclusion: RCDPO affected about one in eight ICU patients. Such patients were sicker and had more comorbidities. The presence of RCDPO was independently associated with higher risk of death. Invasive mechanical ventilation was the only intervention independently associated with greater odds of radiological resolution.

Sodium bicarbonate therapy for metabolic acidosis in critically ill patients: a survey of Australian and New Zealand intensive care clinicians.

OBJECTIVE: To help shape the design of a future double blind placebo-controlled randomised clinical trial of bicarbonate therapy for metabolic acidosis, based on opinions of intensive care clinicians in Australia and New Zealand. DESIGN: An online survey was designed, piloted and distributed electronically to members of the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) mailing list. The survey sought to collect information about choice of placebo, method of bicarbonate administration, and acid-base monitoring. MAIN OUTCOME MEASURES: Responses to six questions in the following domains were sought: 1) solution to be used as placebo; 2) method of administration; 3) target of the intervention; 4) timing of arterial blood gases to monitor the intervention; 5) duration of therapy; and 6) rate of bolus therapy (if selected as the best option). RESULTS: One in every eight ANZICS CTG members completed the survey (118/880, 13.4%). Compound sodium lactate was the preferred solution for placebo (54/118, 45.8%), and continuous infusion of bicarbonate (80/118, 67.8%) was the most frequently selected method of administration. A pH > 7.30 was the preferred target (50/118, 42.4%), while monitoring with arterial blood gas analysis every 2 hours until the target is reached and then every 4 hours was the most favoured option (40/118, 33.9%). The preferred duration of therapy was until the target is achieved (53/118, 44.9%). CONCLUSIONS: This survey offers important insights into the preferences of Australian and New Zealand clinicians in regards to any future randomised controlled trial of bicarbonate therapy for metabolic acidosis in the critically ill.

A comparison of characteristics and outcomes of patients admitted to the ICU with asthma in Australia and New Zealand and United states.

Objective: To compare the characteristics, use of invasive ventilation and outcomes of patients admitted with critical asthma syndrome (CAS) to ICUs in Australia and New Zealand (ANZ), and a large cohort of ICUs in the United States (US). Methods: We examined two large databases of ICU for patients admitted with CAS in 2014 and 2015. We obtained, analyzed, and compared information on demographic and physiological characteristics, use of invasive mechanical ventilation, and clinical outcome and derived predictive models. Results: Overall, 2202 and 762 patients were admitted with a primary diagnosis of CAS in the ANZ and US databases respectively (0.73% vs. 0.46% of all ICU admissions, P < 0.001). A similar percentage of patients received invasive mechanical ventilation in the first 24 h (24.7% vs. 24.4%, P = 0.87) but ANZ patients had lower respiratory rates and higher PaCO2 levels. Overall mortality was low (1.23 for ANZ and 1.71 for USA; P = 0.36) and even among invasively ventilated patients (2.4% for ANZ vs. 1.1% for USA; P = 0.38). However, ANZ patients also had longer length of stay in ICU (43 vs. 37 h, P = 0.001) and hospital (105 vs. 78 h, P = 0.003). Conclusions: Patients admitted to ANZ and USA ICU with CAS are broadly similar and have a low and similar rate of invasive ventilation and mortality. However, ANZ patients made up a greater proportion of ICU patients and had longer ICU and hospital stays. These findings provide a modern invasive ventilation and mortality rates benchmark for future studies of CAS.

Prospective Longitudinal Evaluation of Coagulation with Novel Thromboelastography Technology in Patients After Subarachnoid Hemorrhage: A Pilot Study.

BACKGROUND: There is limited knowledge of whether hypercoagulability is present after subarachnoid hemorrhage (SAH) or about its timing of onset, duration, and severity. To conduct a pilot new-generation thromboelastography (TEG) technology (TEG6s)-based and conventional coagulation test-supported longitudinal assessment of coagulation in patients with SAH. METHODS: We prospectively enrolled patients with nontraumatic SAH on admission from May 2015 to May 2016. We performed TEG6s measurements and conventional coagulation tests on days 1, 2, 3, 5, 7, 10, and 14 and compared them with TEG6s parameters in healthy volunteers. RESULTS: We studied 14 patients and 72 TEG6s measurements. Of these patients, 10 (71.4%) were admitted to the intensive care unit. Mean age was 57.5 (±14.5) years, Acute Physiology and Chronic Health Evaluation III score 58.2 (±26.6), length of hospital stay was 23 (±11.7) days, and mortality was 14.3%. At baseline, conventional coagulation tests were within normal range. However, TEG6s parameters already showed increased coagulability. Thereafter, alpha angle, reaction time, functional fibrinogen level, and maximum amplitude rapidly and significantly increased (P < 0.01) compared with healthy controls. Ten (71.4%) patients demonstrated a >20% increase in coagulability based on TEG6s parameters from their baseline. Moreover, TEG6s hypercoagulability peaked at day 10 and only showed an initial partial decline towards normal by day 14. Similarly, platelet counts and fibrinogen levels increased over this period (P < 0.01) CONCLUSIONS: Using TEG6s technology, we found significant and progressive hypercoagulability in 70% of patients, with an early dominant contribution from hyperfibrinogenemia and increased fibrin formation and partial contribution from thrombocytosis, beginning on the first day, increasing to peak values by day 10, and then partly declining toward normal by day 14.