Sepsis is an inflammatory syndrome with life-threatening organ dysfunction resulting from a dysregulated host response to infection [1, 2]. According to the United States Centers for Disease Control and Prevention (CDC), at least 1.7 million adults in the United States develop sepsis each year. Also, nearly 270,000 people die as a result of sepsis. Furthermore, one out of three death occurrences in hospitals is associated with sepsis . In a retrospective database analysis of 2,466,605 sepsis cases treated as inpatients between January 2010 and September 2016, sepsis, severe sepsis, and septic shock were associated with 6%, 15%, and 34% mortality rates and costs of approximately $16,000, $25,000, and $38,000, respectively .
Based on the 2016 Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock, fundamental management strategies for sepsis or septic shock include early aggressive fluid resuscitation, appropriate early antibiotics, hemodynamic support with vasopressors, and the identification and control of infected sites . The guidelines grade the use of hydrocortisone as a weak recommendation in septic shock unresponsive to fluid resuscitation and vasopressor therapy. Antioxidant supplementation is not part of current sepsis therapy recommendations.
Sepsis can be associated with increased production of reactive oxygen species (ROS) that deplete antioxidant molecules and increase consumption of vitamin C, which correlates with multiorgan failure and death. Intravenous vitamin C may protect several microvascular functions, including capillary blood flow, microvascular permeability barrier, and arteriolar responsiveness to vasoconstrictors and vasodilators . High-dose intravenous (IV) vitamin C has recently been explored as adjunctive therapy in sepsis because of its anti-inflammatory and antioxidant properties [7, 8].
Data have shown conflicting results on the efficacy of using the combination of high-dose vitamin C, thiamine, and hydrocortisone in critically ill patients with sepsis and septic shock. In a retrospective before-after study including 94 patients (47 patients in the treatment group and 47 patients in the control group) with a primary diagnosis of severe sepsis or septic shock, the combination of intravenous vitamin C, moderate-dose hydrocortisone, and thiamine was associated with a significant decrease in-hospital mortality compared with the control group (8.5% versus 40.4%, respectively; P < 0.001). Also, the time to wean off vasopressors was significantly decreased in the treatment group (18.3 ± 9.8 hours versus 54.9 ± 28.4 hours in the control group; P < 0.001) .
However, another retrospective cohort study with a similar study design, in an attempt to replicate the results of the above study by Marik and colleagues, found no significant difference in-hospital mortality between the study groups (40.4% in the treatment group versus 40.4% in the control group; P = 1.000). There was no significant difference in the secondary outcomes as well, including intensive care unit (ICU) mortality, the requirement for renal replacement therapy for acute kidney injury, ICU length of stay, hospital length of stay, and time to vasopressor independence .
Using high-dose Vitamin C alone did not significantly reduce hospital mortality in a retrospective cohort study (46% in the Vitamin C group versus 40% in the control group; P = 0.62). Furthermore, no significant difference was found in the secondary outcomes, including ICU mortality, 90-day mortality, time to shock reversal, doses of vasopressors used during the first four ICU days, duration of initial mechanical ventilation, changes in Sepsis-related Organ Failure Assessment (SOFA) scores and PaO2/FiO2 ratio during the first four ICU days, use of renal replacement therapy (RRT) in patients with acute kidney injury (AKI), and ICU and hospital lengths of stay . It has been proposed that the combination of vitamin C, thiamine, and hydrocortisone has a synergistic effect on reversing the pathophysiologic changes of sepsis, and it cannot be achieved with each drug alone .
Carondelet St. Joseph’s (CSJ) hospital is a 486-bed acute-care hospital established in 1961 in Tucson, Arizona, United States. The hospital has 43 adult ICU beds (23 Medical ICU, 8 Surgical/Trauma ICU, and 12 Neuro ICU). The average ICU patient volume is 23 per day. The critical care service at CSJ hospital is provided through Sound Physicians™, a physician-led healthcare organization based in Tacoma, Washington, United States.
The practice of administering high-dose vitamin C regimen (intravenous vitamin C 1500 mg every six hours; intravenous hydrocortisone 50 mg every six hours; and intravenous thiamine 200 mg every 12 hours) for four days in critically ill patients with sepsis or septic shock was adopted at Carondelet St. Joseph’s hospital in October 2017. The regimen was developed as an order set in the computerized physician order entry (CPOE). We conducted this study to assess the outcomes of this practice at our institution retrospectively.