The CORTICUS Trial [1]
- Multicenter, randomized, double-blind, placebo-controlled trial of 499 patients with septic shock
- 50mg IV hydrocortisone vs placebo every 6 hours for 5 days
- Primary outcome of death at 28 days for pts with no response to a corticotropin stimulation test
Results:
- No significant difference in mortality between the two groups (39.2% vs 36.1% with a p value of 0.69)
- Shock was reversed more quickly in the hydrocortisone group, but with more episodes of new infections (3.3 vs 5.8 days)
Limitation: Study was underpowered (needed 800 patients to be powered correctly)
Conclusion: Hydrocortisone therapy does not improve survival in patients with septic shock, but may reduce duration of vasopressor dependence.
The NICESUGAR Trial [2]
- International, parallel-group, randomized control trial at 42 hospitals
- 6104 patients in an ICU setting
- Intensive glucose control (81 – 108 mg/dL) vs Conventional glucose control (< 180 mg/dL)
- Primary endpoint of death at 90 days
Results:
- Death rate at 90 days of 27.5% in intensive control group vs 24.9% in conventional control group
- Severe hypoglycemia in 6.8% in intensive control group vs 0.5% in conventional control group
- No significant difference in length of stay in ICU or number of days on mechanical ventilation
Conclusion: Intensive glucose control (81 – 108 mg/dL) increased mortality among adults in the ICU vs conventional glucose control (< 180 mg/dL)
The ARDSNet Trial [3]
- Multicenter, randomized control trial
- 861 patients with acute lung injury and/or acute respiratory distress syndrome
- Traditional ventilation (Tidal volume of 12 ml/kg of predicted body weight and a plateau pressure of ≤50 cm H2O) vs ventilation with a lower tidal volume (Tidal volume of 6 ml/kg of predicted body weight and a plateau pressure of ≤30 cm H2O)
- Primary outcomes of death and days without ventilator
Results:
- Trial was stopped early due to drastic mortality benefit from lower tidal volume
- Mortality: Lower TV (31%) vs Traditional TV (39.8%)
- More ventilator free days in the lower tidal volume group (12 vs 10 days)
Conclusion: Lower tidal volume (6mL/kg of predicted body weight) in patients with acute lung injury and acute respiratory distress syndrome results in decreased mortality and decreased number of days on the ventilator.
The SOAP II Trial [4]
- Multicenter, randomized clinical trial of 1679 patients with shock
- Dopamine vs Norepinephrine as first-line vasopressor therapy
- Primary outcome was rate of death at 28 days
Results:
- No statistical difference in mortality (52.5% vs 48.5% with p value of 0.10)
- More arrythmogenic events in the dopamine group (24.1%) vs the norepinephrine group (12.4%)
- Sub-group analysis of patients with cardiogenic shock showed a higher mortality rate with the use of dopamine vs norepinephrine
Conclusion: In patients with shock, the use of dopamine as a first-line vasopressor agent is associated with greater number of adverse events vs norepinephrine.
The VASST Trial [cite source=”pubmed”]18305265[/cite]
- Multicenter, randomized, double-blind trial of 778 patients with septic shock
- Addition of Vasopressin or additional Norepinephrine in patients with septic shock requiring at least 5 mcg/min of norepinephrine
- Primary outcome of mortality rate at 28 days
Results:
- No statistical difference (p value of 0.26) in mortality between Vasopressin (35.4%) vs additional Norepinephrine (39.3%)
- No statistical difference in serious adverse events between the two agents
Conclusion: Vasopressin is comparable to additional norepinephrine when added to norepinephrine therapy in patients with septic shock.
Summary of Five Critical Care Articles For Your Clinical Practice:
- Hydrocortisone therapy does not improve survival in patients with septic shock
- Intensive glucose control increased mortality among adults in the ICU
- Lower tidal volume in patients with ALI and ARDS results in decreased mortality and number of days on the ventilator
- In patients with shock, norepinephrine is the vasopressor of choice
- In patients with septic shock, vasopressin added to norepinephrine can decrease the amount of norepinephrine required
References:
- Sprung CL et al. Hydrocortisone Therapy for Patients with Septic Shock. NEJM 2008. PMID: 18184957
- NICE-SUGAR Study Investigators. Intensive Versus Conventional Glucose Control in Critically Ill Patients. NEJM 2009. PMID: 19318384
- Acute Respiratory Distress Syndrome Network. Ventilation with Lower Tidal Volumes as compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. NEJM 2000. PMID: 10793162
- De Backer D et al. Comparison of Dopamine and Norepinephrine in the Treatment of Shock. NEJM 2010. PMID: 20200382
- Russell JA et al. Vasopressin Versus Norepinephrine Infusion in Patients with Septic Shock. NEJM 2008. PMID: 18305265
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