Iron and erythropoietin to heal and recover after intensive care (ITHRIVE): A pilot randomised clinical trial.

Objective: To determine the feasibility of a pivotal randomised clinical trial of intravenous (IV) iron and erythropoietin in adult survivors of critical illness with anaemia requiring treatment in the intensive care unit. Design: An investigator-initiated, parallel group, placebo-controlled, randomised feasibility trial. Setting: A tertiary intensive care unit (ICU) in Perth, Western Australia. Participants: Adults with anaemia (haemoglobin <100 g/L), requiring ICU-level care for more than 48 h, and likely to be ready for ICU discharge within 24 h. Interventions: A single dose of IV ferric carboxymaltose and Epoetin alfa (active group) or an equal volume of 0.9% saline (placebo group). Main outcome measures: Study feasibility was considered met if the pilot achieved a recruitment rate of ≥2 participants per site per month, ≥90% of participants received their allocated study treatment, and≥ 90% of participants were followed up for the proposed pivotal trial primary outcome - days alive and at home to day 90 (DAH90). Results: The 40-participant planned sample size included twenty in each group and was enrolled between 1/9/2021 and 2/3/2022. Participants spent a median of 3.4 days (interquartile range 2.8-5.1) in the ICU prior to enrolment and had a mean baseline haemoglobin of 83.7 g/L (standard deviation 6.7). The recruitment rate was 6.7 participants per month [95% confidence interval (CI) 4.8-9.0], DAH90 follow-up was 100% (95% CI 91.2%-100%), and 39 (97.5%, 95% CI 86.8%-99.9%) participants received the allocated study intervention. No serious adverse events were reported. Conclusion: The iron and erythropoietin to heal and recover after intensive care (ITHRIVE) pilot demonstrated feasibility based on predefined participant recruitment, study drug administration, and follow-up thresholds.

Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: the randomised, placebo-controlled, restoration of gut microflora in critical illness trial (ROCIT).

PURPOSE: In adults requiring treatment in an intensive care unit, probiotic therapy using Lactobacillus plantarum 299v may reduce nosocomial infection. The aim of this study was to determine whether early and sustained L. plantarum 299v therapy administered to adult ICU patients increased days alive and at home. METHODS: A multicentre, parallel group, placebo-controlled, randomised clinical trial was conducted. Adult patients within 48 h of intensive care admission and expected to require intensive care beyond the day after recruitment were eligible to participate. L plantarum 299v or placebo were administered immediately after enrolment and continued for 60 days. The primary outcome was days alive and out of hospital to Day 60 (DAOH60). Secondary outcomes included nosocomial infections. RESULTS: The median [interquartile range (IQR)] number of DAOH60 in the probiotic (n = 110) and placebo group (n = 108) was 49.5 (IQR 37.0-53.0) and 49.0 (IQR 43.8-53.0) respectively, between-group difference of 0.0 [95% confidence interval (CI) - 6.10 to 7.1, P = 0.55]. Nosocomial infection occurred in 8 (7.3%) and 5 (4.6%) of the probiotic and placebo group participants, respectively, odds ratio 1.62 (95% CI 0.51-5.10), P = 0.57. There were no serious, or probiotic-associated adverse events. CONCLUSION: Early and sustained untargeted administration of probiotic therapy with Lactobacillus plantarum 299v to adult patients admitted to the ICU is safe, but not associated with improved patient outcomes.

Study protocol for the safety and efficacy of probiotic therapy on days alive and out of hospital in adult ICU patients: the multicentre, randomised, placebo-controlled Restoration Of gut microflora in Critical Illness Trial (ROCIT).

INTRODUCTION: The effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain. METHODS AND ANALYSIS: The Restoration Of gut microflora in Critical Illness Trial (ROCIT) study is a multicentre, randomised, placebo-controlled, parallel-group, two-sided superiority trial that will enrol 220 patients in five ICUs. Adult patients who are within 48 hours of admission to an ICU and are expected to require intensive care beyond the next calendar day will be randomised in a 1:1 ratio to receive early and sustained Lactobacillus plantarum 299v probiotic therapy in addition to usual care or placebo in addition to usual care. The primary endpoint is days alive and out of hospital to day 60. ETHICS AND DISSEMINATION: ROCIT has been approved by the South Metropolitan Health Service Human Research Ethics Committee (ref: RGS00000004) and the St John of God Health Care Human Research Ethics Committee (ref: 1183). The trial results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ANZCTR12617000783325); Pre-results.

Does femoral venous pressure measurement correlate well with intrabladder pressure measurement? A multicenter observational trial.

PURPOSE: To investigate if femoral venous pressure (FVP) measurement can be used as a surrogate measure for intra-abdominal pressure (IAP) via the bladder. METHODS: This was a prospective, multicenter observational study. IAP and FVP were simultaneously measured in 149 patients. The effect of BMI on IAP was investigated. RESULTS: The incidences of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) were 58 and 7% respectively. The mean APACHE II score was 22 ± 10, SAPS 2 score 42 ± 20, and SOFA score 9 ± 4. The mean IAP was 11.2 ± 4.5 mmHg versus 12.7 ± 4.7 mmHg for FVP. The bias and precision for all measurements were -1.5 and 3.6 mmHg respectively with the lower and upper limits of agreement being -8.6 and 5.7. When IAP was above 20 mmHg, the bias between IAP and FVP was 0.7 with a precision of 2.0 mmHg (lower and upper limits of agreement -3 and 4.6 respectively). Excluding those with ACS, according to the receiver operating curve analysis FVP = 11.5 mmHg predicted IAH with a sensitivity and specificity of 84.8 and 67.0% (AUC of 0.83 (95% CI 0.81-0.86) with P < 0.001). FVP = 14.5 mmHg predicted IAP above 20 mmHg with a sensitivity of 91.3% and specificity of 68.1% (AUC 0.85 (95% CI 0.79-0.91), P < 0.001). Finally, at study entry, the mean IAP in patients with a BMI less then 30 kg/m(2) was 10.6 ± 4.0 mmHg versus 13.8 ± 3.8 mmHg in patients with a BMI ≥ 30 kg/m(2) (P < 0.001). CONCLUSIONS: FVP cannot be used as a surrogate measure of IAP unless IAP is above 20 mmHg.