ICU Journal Club – VICCSS Study Dr Swapnil Pawar
Dr Swapnil Pawar & Dr Jose Chacko
High dose vitamin C has a strong biological rationale in post-cardiac surgery vasoplegia. Vitamin C scavenges reactive oxygen species, which likely contribute to vasoplegia after cardiac surgery, stimulates norepinephrine synthesis, decreases the incidence of atrial fibrillation, cardiac enzyme release, and the level of markers of oxidative stress. In addition, cardiac surgery patients have decreased vitamin C levels compared to preoperative values suggesting increased consumption and/or dilution.
high dose intravenous vitamin C has recently been used to treat vasodilatory septic shock which is also a vasodilatory shock. Such studies used high dose (6000 mg per day in four divided doses) vitamin C in association with thiamine and hydrocortisone and found a decrease in vasopressor therapy duration. because corticosteroid or thiamine therapy for cardiac surgery patients has been shown to have no effect on hemodynamic or clinical outcomes, authors decided to use high dose intravenous vitamin C monotherapy in this study.
to investigate the effect of high dose vitamin C in patients with vasoplegia after cardiac surgery, with the aim of establishing whether larger trials could both be successfully conducted and justified by promising preliminary findings.
in patients admitted to ICU after cardiac surgery, high dose vitamin C therapy would be associated with earlier resolution of postoperative vasoplegia.
Methods – a randomized, two-centre, double-blind, feasibility, safety and physiological efficacy pilot trial comparing high-dose vitamin C to placebo in the treatment of vasoplegia in patients admitted to the intensive care unit (ICU) after cardiac surgery.
Settings – The study was conducted in two tertiary ICUs, one in Australia and one in New Zealand
Design– randomly assigned eligible patients to receive either vitamin C or placebo, with a 1:1 ratio. Randomization was performed by means random number sequences utilizing permuted blocks of variable size and allocation was concealed using sequentially numbered sealed envelopes. Each envelope contained the patient’s study number and the study arm allocation.
Inclusion Criteria –
Exclusion Criteria –
Sample Size – Pilot, feasibility study – to enrol 50 patients over two sites. Such a study would provide a greater than 78% power to detect a difference in the duration of vasopressor therapy equal to that reported in a recent study of septic vasoplegia.
Patients -Authors screened 456 patients from November 8, 2017, to October 29, 2018, and enrolled 50 patients (25 patients in each group) in the study.
Statistical Analysis– an intention-to-treat basis, p<0.05 considered significant.
Results- Baseline- Median age was 67.0 years in the vitamin C group and 64.0 years in the placebo group. Median EuroSCORE was 5.0 in both groups and 96.0% of the patients received norepinephrine. The median baseline norepinephrine equivalent dose was the same in both groups at 0.06 µg kg-1 min-1 norepinephrine, equivalent to approximately 5 µg min-1 in an 80 kg patient
Primary Outcomes– There was no difference between the two groups for time to postoperative vasoplegia resolution (P=0.51) 27hours vs 34.7 hours in placebo.
Secondary Outcomes- There was no statistical difference in the total norepinephrine equivalent dose administered on first 2 calendar days after randomization)-Median ICU length of stay was similar in the two groups-MAP, heart rate, cumulative norepinephrine equivalent dose and fluid administration in the first three days showed no difference between the two groups.
Conclusion- In a pilot double-blind randomized trial in cardiac surgery patients with postoperative vasoplegia, the resolution of the vasoplegic state occurs on average within 1.5 days. High dose intravenous vitamin C does not significantly decrease the duration of vasopressor therapy and appeared unlikely to have a clinically important impact on this outcome.