It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock.OBJECTIVE To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTSMulticenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019.INTERVENTIONS Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. MAIN OUTCOMES AND MEASURESThe primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality.RESULTS Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported. CONCLUSIONS AND RELEVANCEIn patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone.

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Objectives: To evaluate what proportion of unplanned ICU admissions from hospital wards occurred after rapid response team review and compare baseline characteristics and outcomes of patients admitted after rapid response team review with non-rapid response team-related admissions. Design: Multicenter binational retrospective cohort study. Setting: One-hundred seventy-eight ICUs across Australia and New Zealand. Patients: All adults (≥ 17 yr) in the Australian and New Zealand Intensive Care Society Adult Patient Database between 2012 and 2017. Interventions: None. Measurements and Main Results: Among 97,181 unplanned ICU admissions from the ward, prior rapid response team review occurred in 55,084 cases (56.7%). Rapid response team patients were slightly older (65.4 [16.9] vs 63.3 [18]), had a higher Acute Physiology and Chronic Health Evaluation III score (64.6 [27.1] vs 54.7 [25.3]) and more frequently had limitations of medical treatment (13.1% vs 8.5%) compared with patients with no rapid response team review. The strongest independent associations with ICU admission following rapid response team review included age, ICU admission diagnosis (especially sepsis-, neurologic-, respiratory-, and cardiovascular-related), tertiary ICU status, and presence of limitations of medical treatment (p < 0.0001 all comparisons). Rapid response team-related ICU admissions had a longer median ICU (2.4 d [1.2–4.6 d] vs 2.1 d [1.0–4.2 d]) and hospital (12.8 d [7.0–23.6 d] vs 10.8 d [5.9–20.3 d]) length of stay, and were more likely to die in the ICU (12.3% vs 7.5%) and in-hospital (20.8% vs 13.5%) (p < 0.0001). After adjusting for illness severity and institution, patients admitted following rapid response team review stayed longer in hospital but were not at increased risk of dying in-hospital (adjusted odds ratio, 1.03; 0.98–1.07). Conclusions: In Australia and New Zealand, hospital ward patients admitted to ICU following rapid response team review represent the majority of ward-based ICU admissions, are more chronically and acutely ill, and more frequently have sepsis than those admitted from the ward without rapid response team review. Their unadjusted outcomes are worse, but after adjustment their mortality is similar.

Prospective identification of patients requiring palliative care may be possible prior to MET involvement. This may allow more timely and appropriate end-of-life discussions.