Articles That Matter

Young P, Bailey M, Beasley R, et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial. JAMA 2015; :1.

Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. Ann Intern Med 2015; 163:519.

Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam JS, Lim WS. Effect of corticosteroid therapy on influenza-related mortality: a systematic review and meta-analysis. J Infect Dis 2015; 212:183.

Frat JP, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015; 372:2185.

Jain S, Self WH, Wunderink RG, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med 2015; 373:415.


Dellinger RP et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med 2013;41(2):580-637.

Comments: Quick summary for the ED: Find the source of infection. Control it. Get blood cultures. Check lactate. Give antibiotics. Give crystalloid 30mL/kg. Give norepinephrine if still hypotensive. Limit transfusions. Give low tidal volumes in ARDS. Limit sedation and paralytics. PMID: 23353941

Landmark Articles

Mouncey PR,  Osborn TM, Power GS, et al for the ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. NEJM 2015; 372(14):1301-11.

CONCLUSIONS: In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. PMID: 25776532

Comments: This UK study found no difference in mortality for early goal-directed therapy (EGDT) vs. usual care in septic shock patients. Mortality was around 29% in both groups. EGDT was more costly.


Holst LB, Haase N, Wetterslev J et al for the TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. doi: 10.1056/NEJMoa1406617. Epub 2014 Oct 1.

CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. PMID: 25270275

Comments: We know that in critically ill patients, a restrictive vs. liberal transfusion strategy was as effective, except perhaps in those with ACS but what about patients with septic shock? The mortality rates were the same, and the 7.o g/dL vs. 9.0 g/dL group got only one unit of blood as opposed to 4.  In septic shock patients, the transfusion trigger should be around 7 g/dL.


Asfar P, Meziani F, Hamel JF et al for the SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014 Apr 24;370(17):1583-93. doi: 10.1056/NEJMoa1312173. Epub 2014 Mar 18.

CONCLUSIONS: Targeting a mean arterial pressure of 80 to 85 mm Hg, as compared with 65 to 70 mm Hg, in patients with septic shock undergoing resuscitation did not result in significant differences in mortality at either 28 or 90 days. PMID: 24635770

Comments: Surviving Sepsis recommends a MAP target of 65, but is a higher MAP better?  Mortality was the same in each group, but the higher target had more atrial fibrillation.  A MAP of 65 is good enough in septic shock.  I wish they could have changed the acronym to SEPSISMAP, which would have been much cooler than SEPSISPAM.


ARISE Investigators and ANZICS Trial Group. Goal-Directed Resuscitation for Patients with Early Septic Shock. NEJM 2014; 371:1496-1506.

CONCLUSIONS: In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. PMID: 25272316

Comments: There was no difference in mortality in septic shock patients with EGDT vs. usual care in Australia and New Zealand. Overall mortality was low, around 18.5% in both groups.


The ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. NEJM 2014; 370:1683-93.

CONCLUSIONS: In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. PMID: 24635773

Comments: There were three groups in this RCT: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; and usual care.  Mortality was 21%, 18.2%, and 18.9% in the three groups, respectively (not statistically different).


DeBacker D, Aldecoa C, Njimi H et al. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med 2012; 40(3):725-30.

CONCLUSIONS: In patients with septic shock, dopamine administration is associated with greater mortality and a higher incidence of arrhythmic events compared to norepinephrine administration. PMID: 22036860

Comments: The conclusion: "In patients with septic shock, dopamine administration is associated with greater mortality and a higher incidence of arrhythmic events compared to norepinephrine administration."


Jones AE, Shapiro NI, Trzeciak S et al for EMShockNet investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 2010;303(8):739-46.

CONCLUSION: Among patients with septic shock who were treated to normalize central venous and mean arterial pressure, additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality. PMID: 20179283

Comments: Part of EGDT involved invasive measurement of central venous oxygen saturation (ScvO2). This study compared resuscitation of septic shock patients to normalize central venous pressure, mean arterial pressure, and -  either central venous oxygen saturation (ScvO2) to 70% or lactate clearance of 10%.  They found that there was no difference in mortality. There was a non-significant trend for improved mortality in the lactate clearance group: 17% lactate clearance vs. 23% ScvO2.


Sprung CL, Annane D, Keh D et al for the CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008 Jan 10;358(2):111-24. doi: 10.1056/NEJMoa071366.

CONCLUSIONS: Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. PMID: 18184957

Comments: Annane published an important paper in 2002 that showed a mortality benefit for septic shock patients treated with hydrocortisone.  However, in this study, there was no mortality benefit but time to resolution of shock was faster in patients treated with hydrocortisone 50mg IV Q6H tapered over 6 days.  Patients who respond to fluids and vasopressors do not have a mortality benefit from hydrocortisone in septic shock.


Kumar A et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34(6):1589-96.

CONCLUSIONS: Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypotension. PMID: 16625125

Comments: The odds ratio of death was 1.119 per hour delay in sepsis patients. Mortality increased 7.6% per hour delay in giving appropriate antibiotics to sepsis patients who developed hypotension. Median time to antibiotics after patients were noted to be hypotensive was 6 hours. The study is limited by its retrospective design but is likely the best we will get on this topic.


Finfer S, Bellomo R, Boyce N et al for the SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004 May 27;350(22):2247-56.

CONCLUSIONS: In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days.

Comments: Are crystalloids or albumin better for volume repletion in a heterogeneous ICU population?  There was no difference, except in traumatic brain injury patients, who fared worse with albumin.


Rivers E, Nguyen B, Havstad S et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM 2001;345(19):1368-77.

CONCLUSIONS: Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock. PMID: 11794169

Comments: A sepsis protocol started in the ED improved mortality in septic shock patients (30.5%), as opposed to usual care (46.5%).  As later work has shown, many of the components of this protocol, especially the invasive aspects, were not important to improving survival.  Early source control, antibiotics, and fluids were most important.


ARDSNet Investigators. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. NEJM 2000;342:1301-1308.

CONCLUSIONS: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use. PMID: 10793162

Comments: Mechanical ventilation of patients with acute lung injury with a low tidal volume (6mL/kg based on ideal body weight vs. 12mL/kg) reduced mortality. Number needed to treat is 11.4.  This study completely changed mechanical ventilation in ARDS.


ANZICS Trial Group. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Lancet 2000;356: 2139–43.

CONCLUSIONS: Administration of low-dose dopamine by continuous intravenous infusion to critically ill patients at risk of renal failure does not confer clinically significant protection from renal dysfunction. PMID: 11191541

Comments: Low dose dopamine in critically ill patients does not confer protection against renal dysfunction.


Hebert PC, Wells G, Blajchman MA et al. A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care, TRICC. NEJM 1999; 340:409-417.

CONCLUSIONS: A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina. PMID: 9971864

Comment: Transfusion at a hemoglobin trigger of 7.0g/L vs 10g/L reduced mortality in lower acuity ICU patients, with the possible exception of those with acute MI or unstable angina.


Brochard L, Mancebo J, Wysocki M et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995;333(13):817-22.

CONCLUSIONS: In selected patients with acute exacerbations of chronic obstructive pulmonary disease, noninvasive ventilation can reduce the need for endotracheal intubation, the length of the hospital stay, and the in-hospital mortality rate. PMID: 7651472

Comments: Non-invasive ventilation markedly reduced intubation rates (NNT = 2), length of stay, and mortality in this RCT with about 80 patients.


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