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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 14:47, 10 August 2018
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| fulltexturl=http://journal.chestnet.org/article/S0012-3692(16)62564-3/fulltext | | fulltexturl=http://journal.chestnet.org/article/S0012-3692(16)62564-3/fulltext | ||
| pdfurl=http://journal.chestnet.org/article/S0012-3692(16)62564-3/pdf | | pdfurl=http://journal.chestnet.org/article/S0012-3692(16)62564-3/pdf | ||
| status= | | status=published | ||
| subspecialty=Critical Care | | subspecialty=Critical Care | ||
| otherSubspecialty1=Infectious Disease | | otherSubspecialty1=Infectious Disease | ||
| Line 22: | Line 22: | ||
| intervention2=Hydrocortisone | | intervention2=Hydrocortisone | ||
| intervention3=Thiamine | | intervention3=Thiamine | ||
| briefDesignDescription= | | briefDesignDescription=Hydrocortisone, Vit C, and thiamine in severe sepsis and septic shock | ||
| briefResultsDescription= | | briefResultsDescription=Pilot study with impressive findings, low-quality data | ||
| trainingLevel=Resident | | trainingLevel=Resident | ||
}} | }} | ||
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==Bottom Line== | ==Bottom Line== | ||
In this | In this pilot trial that matched patients receiving an intervention to historical controls, 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 before the protocol is incorporated into routine practice. | ||
==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 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 | 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 controls 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 | 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 extremely cautious in interpreting these findings. For context, the use of historical controls has been identified as the second-lowest level of evidence quality in the Global Health Evidence Framework.<ref>[https://www.ncbi.nlm.nih.gov/books/NBK121300/table/appb.t21/ Shekelle PG, et al. Global Health Evidence Framework. ''Southern California Evidence-based Practice Center.'' 2013.]</ref> The generalizability is also limited due to the single centre design. As a feasibility 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== | ||
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==Design== | ==Design== | ||
* Single center | * Single center intervention study matching to historical controls | ||
* N=97 | * N=97 | ||
** Vitamin C Protocol (n=47) | ** Vitamin C Protocol (n=47) | ||
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* Hydrocortisone 50 mg every 6h for 7 days or until ICU discharge followed by a taper over 3 days | * 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 | * 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 | ** Piggyback 50 mL D5W or 0.9% NaCl over 30 min infusion | ||
==Outcomes== | ==Outcomes== | ||
''Presented as | ''Presented as treatment vs. control groups'' | ||
===Primary Outcome=== | ===Primary Outcome=== | ||
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** 60% received with hydrocortisone | ** 60% received with hydrocortisone | ||
** Thiamine exposure not reported | ** Thiamine exposure not reported | ||
* Small sample size | * Small sample size and use of historical controls introduces a tremendous risk of '''bias''' | ||
* Decreased '''external validity''' due to single centre | * Decreased '''external validity''' due to single centre | ||