Research for IV Protocol:

1. Combined vitamin C, hydrocortisone, and thiamine therapy for patients with severe pneumonia who were admitted to the intensive care unit: Propensity score-based analysis of a before-after cohort study

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2.2. Treatment protocol

In June 2017, experimental and emerging clinical data led our institution to adopt the vitamin C protocol as a routine adjunct therapy for severe pneumonia. The protocol consists of intravenous vitamin C (1.5 g every 6 h for 4 days), hydrocortisone (50 mg every 6 h for 7 days followed by a taper over 3 days), and intravenous thiamine (200 mg every 12 h for 4 days) [17]. We decided to administer 6 g of vitamin C per day (divided into four equal doses) because intravenous vitamin C at a dose of 6 g/day normalizes leukocyte vitamin C levels in respiratory infections [21]. The vitamin C protocol was not used when the patient had nosocomial pneumonia or a do not resuscitate order. During the control period, the patients with severe pneumonia did not receive either vitamin C or thiamine. However, they did sometimes receive corticosteroids at the discretion of the attending physician.

All patients were managed according to the therapeutic recommendations in the Surviving Sepsis Campaign Guidelines and the lung-protective ventilation strategy [22, 23]. All patients were treated with antibiotics according to international guidelines [24]. Apart from the administration of the vitamin C protocol during the treatment period, the ICU treatment protocols in the before and after study periods were identical. There were also no known significant changes to our study population (i.e., type of admission, criteria for admission, or comorbidities before admission).

Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study

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RESULTS:

There were 47 patients in both treatment and control groups, with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared with 40.4% (19 of 47) in the control group (P < .001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI, 0.04-0.48; P 1⁄4 .002). The Sepsis-Related Organ Failure Assessment score decreased in all patients in the treatment group, with none developing progressive organ failure. All patients in the treatment group were weaned off vasopressors, a mean of 18.3  9.8 h after starting treatment with the vitamin C protocol. The mean duration of vasopressor use was 54.9  28.4 h in the control group (P < .001).

ICU Treatment Protocol

ICU Treatment Protocol The overall treatment of patients with sepsis during the control and treatment periods was similar except for the administration of the combination of vitamin C, hydrocortisone, and thiamine during the treatment period.42 There were no known significant changes to our ICU protocols, referral patterns, or patient population during the study period. During the control period patients received hydrocortisone (50 mg every 6 h) at the discretion of the attending physician.26,42,43 As per standard operating procedure in our ICU, all patients with sepsis and septic shock are started empirically on broad-spectrum antibiotics, which are then deescalated according to microbiologic data and clinical progress44; are treated according to a conservative, physiologically based fluid and vasopressor strategy 45,46; and are ventilated according to a lung-protective strategy,46,47 avoiding hyperoxia 48 and with the limited use of sedative agents (preferred agent, dexmedetomidine).49 Norepinephrine is the vasopressor of first choice and is titrated to a dose of 20 mg/min, targeting a mean arterial pressure > 65 mm Hg. In patients failing to achieve this target, fixed-dose vasopressin was then added at 0.04 units/min followed by phenylephrine or epinephrine.42,45 Patients receive enteral nutrition with a whey-based formula (Vital 1.2; Abbott), using an intermittent bolus protocol that is started 24 h after ICU admission; once clinical stability is achieved,50,51 they receive deep venous thrombosis prophylaxis with both enoxaparin (or heparin in patients with a calculated creatinine clearance < 30 mL/min) and sequential compression, and we allow permissive hyperglycemia.52 Routine stress ulcer prophylaxis is not administered.53

During the treatment period consecutive patients with a primary admitting diagnosis of severe sepsis or septic shock and a PCT level > 2 ng/mL were treated with intravenous vitamin C (1.5 g every 6 h for 4 days or until ICU discharge), hydrocortisone (50 mg every 6 h for 7 days or until ICU discharge followed by a taper over 3 days), as well as intravenous thiamine (200 mg every 12 h for 4 days or until ICU discharge).The vitamin C was administered as an infusion over 30 to 60 min and mixed in a 100- mL solution of either dextrose 5% in water (D5W) or normal saline. Intravenous thiamine was given as a piggyback in 50 mL of either D5W or normal saline and was administered as a 30-min infusion. We attempted to determine the vitamin C level prior to the first dose of vitamin C. The vitamin C assay was performed at LabCorp by high-pressure liquid chromatography with electrochemical detection. The specimens were collected in a serum separation gel tube, protected from light, and transported on ice. The specimens were frozen prior to transport to the local reference laboratory (LabCorp).

Step One:

Combined Vitamin C, Hydrocortisone, and Thiamine IV Protocol

• intravenous vitamin C: (1.5 g every 6 h for 4 days)
• intravenous hydrocortisone: (50 mg every 6 h for 7 days followed by a taper over 3 days)
• intravenous thiamine: (200 mg every 12 h for 4 days)

Day 1:

• • IV Vitamin C (1.5 g every 6 h)
  • IV Hydrocortisone (50 mg every 6 h)
  • IV Thiamine (200 mg every 12 h)

Day 2:

• • IV Vitamin C (1.5 g every 6 h)
  • IV Hydrocortisone (50 mg every 6 h)
  • IV Thiamine (200 mg every 12 h)

Day 3:

• • IV Vitamin C (1.5 g every 6 h)
  • IV Hydrocortisone (50 mg every 6 h)
  • IV Thiamine (200 mg every 12 h)

Day 4:

• • IV Vitamin C (1.5 g every 6 h)
  • IV Hydrocortisone (50 mg every 6 h)
  • IV Thiamine (200 mg every 12 h)

Day 5:

• • IV Hydrocortisone (50 mg every 6 h)

Day 6:

• • IV Hydrocortisone (50 mg every 6 h)

Day 7:

• • IV Hydrocortisone (50 mg every 6 h)

Day 8:

• • Taper Hydrocortisone 

Day 9:

• • Taper Hydrocortisone 

Day 10:

• • Taper Hydrocortisone

Step Two (until blood markers normalize):

Oral Supplementation for Acute Infection Protocol

• • 20,000 – 40,000 IU vitamin D 1x/day
  • 8,000mg NAC divided into at least 2 doses 
  • 44-50mg Zinc 1x/day
    • 4 mg Copper
  • 600mcg Selenium 1x/day
  • 8g Vitamin C 3x/day (monitor bowels and back off 50% if not tolerated)
  • 10,000 IU Vitamin A (300 mcg retinol) 1xday