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Hydrocortisone, Vitamin C, and Thiamine in Severe Sepsis and Septic Shock: Difference between revisions
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Hydrocortisone, Vitamin C, and Thiamine in Severe Sepsis and Septic Shock (view source)
Revision as of 18:27, 9 August 2018
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==Bottom Line== | ==Bottom Line== | ||
In this | In this pre-post pilot trial, the combination of high dose Vitamin C, mid-dose hydrocortisone, and thiamine was associated with positive outcomes for sepsis/shock. The quality of evidence from this trial is overall low and multicenter RCTs are needed to confirm these findings. | ||
==Major Points== | ==Major Points== | ||
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Multiple RCTs have investigated the potential role for steroid therapy in patients with septic shock. The [[Annane Trial]] in 2002 demonstrated a short-term mortality benefit with IV hydrocortisone and fludrocortisone among patients with evidence of adrenal insufficiency on ACTH stimulation testing. [[CORTICUS]] in 2008 investigated hydrocortisone in patients with and without adrenal insufficiency and found no benefit in either subgroup with suggestion of increased infection rates in patients receiving hydrocortisone. Most recently [[HYPRESS]], published 2016, demonstrated little benefit in advancing septic shock but no excess infections in the treatment group. This trial was conducted between [[CORTICUS]] and [[HYPRESS]]. | Multiple RCTs have investigated the potential role for steroid therapy in patients with septic shock. The [[Annane Trial]] in 2002 demonstrated a short-term mortality benefit with IV hydrocortisone and fludrocortisone among patients with evidence of adrenal insufficiency on ACTH stimulation testing. [[CORTICUS]] in 2008 investigated hydrocortisone in patients with and without adrenal insufficiency and found no benefit in either subgroup with suggestion of increased infection rates in patients receiving hydrocortisone. Most recently [[HYPRESS]], published 2016, demonstrated little benefit in advancing septic shock but no excess infections in the treatment group. This trial was conducted between [[CORTICUS]] and [[HYPRESS]]. | ||
Vitamin C | Vitamin C is an antioxidant that is vital to immune function. Its role in sepsis, and if it may synergistically reduce inflammation along with hydrocortisone, is unknown. Published in 2017 in Chest, Marik and colleagues sought to understand the potential role of Vitamin C, hydrocortisone, and thiamine in severe sepsis and septic shock. This small, single-center trial administered these agents to 47 patients and compared them to historical controls. The treatment group as compared to the historical cohort showed an absolute decrease of hospital mortality of 32% (P<0.001) as well as statistically significant decreases in duration of vasopressor therapy, the need of renal replacement therapy, procalcitonin clearance and decreases in SOFA score. | ||
There were a number of limitations with this trial. The small sample size increases the risk of bias with the effect. The lack of a concurrent comparator group also must make us cautiously interpret these findings. The generalizability is also limited due to the single centre design. As a feasiblity study, this now makes way for a larger RCT to be conducted to test this in a wider population. | There were a number of limitations with this trial. The small sample size increases the risk of bias with the effect. The lack of a concurrent comparator group also must make us cautiously interpret these findings. The generalizability is also limited due to the single centre design. As a feasiblity study, this now makes way for a larger RCT to be conducted to test this in a wider population. By itself, this study is low-quality evidence and should not be used to drive management of patients with severe sepsis and septic shock. | ||
==Guidelines== | ==Guidelines== | ||
{{no guidelines|2018|12}} | |||
==Design== | ==Design== | ||
* | * Single center, pre-post/case-control study | ||
* N= 97 | * N=97 | ||
** Vitamin C Protocol (n=47) | ** Vitamin C Protocol (n=47) | ||
** Historical comparator (n=47) | ** Historical comparator (n=47) | ||
* Setting: Single tertiary care hospital in Eastern Virginia, USA | * Setting: Single tertiary care hospital in Eastern Virginia, USA | ||
* Enrollment: January 2016 and July 2016 | * Enrollment: January 2016 and July 2016 | ||
* Mean follow-up: | * Mean follow-up: Not defined, but most outcomes were at 4 days | ||
* Primary outcome: Hospital survival | * Primary outcome: Hospital survival | ||
==Population== | ==Population== | ||
===Inclusion Criteria=== | ===Inclusion Criteria=== | ||
* | * Consecutive patients admitted to the Eastern Virginia Medical School Critical Care Medicine service | ||
* | * Primary diagnosis of severe sepsis or septic shock | ||
* | * Procalcitonin (PCT) level ≥2 ng/mL | ||
===Exclusion Criteria=== | ===Exclusion Criteria=== | ||
* <18 years of age | * <18 years of age | ||
* | * Pregnant | ||
* | * Patients with limitations of care (not further described) | ||
===Baseline Characteristics=== | ===Baseline Characteristics=== | ||
''Treatment group displayed'' | ''Treatment group displayed'' | ||
* Age | * Demographics: Age 58 years, 57% male | ||
* Comobidities, No.(%) | * Comobidities, No.(%) | ||
** None: 2 (4) | ** None: 2 (4) | ||
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* Mechanical ventilation, No.(%): 22 (47) | * Mechanical ventilation, No.(%): 22 (47) | ||
* Vasopressors, No.(%): 22 (46) | * Vasopressors, No.(%): 22 (46) | ||
* Procalcitonin, median(IQR), ng/ml: 25.8 (5.8-93.4) | * Procalcitonin, median (IQR), ng/ml: 25.8 (5.8-93.4) | ||
* Day 1 SOFA, mean±SD: 8.3 ± 2.8 | * Day 1 SOFA, mean±SD: 8.3 ± 2.8 | ||
* APACHE II, mean±SD: 22.1 ± 6.3 | * APACHE II, mean±SD: 22.1 ± 6.3 | ||
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* WBC, mean±SD,×10^9: 20.6 ± 13.5 | * WBC, mean±SD,×10^9: 20.6 ± 13.5 | ||
* Lactate, mean±SD mM: 2.7 ± 1.5 | * Lactate, mean±SD mM: 2.7 ± 1.5 | ||
* Creatinine, mean±SD,mg/dL(mcmol/L): 1.9 ± 1.4(168 ± 124) | * Creatinine, mean±SD, mg/dL(mcmol/L): 1.9 ± 1.4(168 ± 124) | ||
==Interventions== | ==Interventions== | ||
* | * Intravenous vitamin C 1.5g every 6h for 4 days or until ICU discharge | ||
** | ** Mixed in 100 mL D5W or 0.9% NaCl, infused over 30-60min | ||
* | * Hydrocortisone 50 mg every 6h for 7 days or until ICU discharge followed by a taper over 3 days | ||
* | * Intravenous thiamine 200 mg every 12h for 4 days or until ICU discharge | ||
** | ** Piggyback 50 mL D5W or 0.9%NaCl over 30 min infusion | ||
==Outcomes== | ==Outcomes== | ||
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; ICU Length Of Stay, median(IRQ),d | ; ICU Length Of Stay, median(IRQ),d | ||
: 4(3-5) vs. 4(4-10) | : 4 (3-5) vs. 4 (4-10) | ||
; Serum Procalcitonin clearance over the first 72h, median | ; Serum Procalcitonin clearance over the first 72h, median (IQR) | ||
: 86.4(80.1-90.8) vs. 33.9(–62.4 to 64.3), P<0.001 | : 86.4% (80.1-90.8) vs. 33.9% (–62.4 to 64.3), P<0.001 | ||
; Change in SOFA score over the first 72h | ; Change in SOFA score over the first 72h | ||