Supplemental Table 1: Concentrated Review of Major Critical Care Trials

Focus Study Findings Journal/Year

Sepsis PHEONIX In distributive shock, pyridoxalated Hb solution ↓ need of vasopressors but ↑ mortality

CCM 2015 (1)

AROISS Acetaminophen 1g every 6 hours for 3 days from ICU admission may ↓ oxidative injury and ↑ renal function

CCM 2015 (2)

ProMISe Strict EGDT protocol did not improve mortality in patients with septic shock after antibiotics and fluids

CCM 2015 (3)

Trzeciak Inhaled nitric oxide at 40 ppm does not augment microcirculatory perfusion

CCM 2014 (4)

TRISS In septic shock, no mortality/ischemia difference between Hb of 7 g/dL versus 9 g/dL

NEJM 2014 (5)

ARISE EGDT does not ↓ 90-day mortality/ LOS/ RRT/vent days NEJM 2014 (6)ProCESS No difference in EGDT vs usual care in sepsis NEJM. 2014

(7)SEPSISPAM In septic shock, higher MAPs (80-85) ↑ risk of atrial

fibrillation and does not ↓ mortalityNEJM. 2014 (8)

ALBIOS Daily albumin in severe sepsis does not ↓ mortality/ RRT/ vent days

NEJM 2014 (9)

ALBIOS-II Presepsis is a useful prognostic measure in patients with severe sepsis/septic shock. Procalcitonin was not

CC 2014 (10)

ESMOLOL Esmolol ↓’s heart rate without ↑ adverse events in tachycardic patients with septic shock.

JAMA 2013 (11)

STATIN-VAP Adjunctive simvastatin in patients with suspected VAP does not improve mortality, MVD, SOFA score

JAMA 2013 (12)

PROWESS-SHOCK

Xigris (drotrecogin alfa) does not ↑survival NEJM 2012 (13)

ETOMIDATE Adrenal insufficiency ↑’s with etomidate. Moderate-dose hydrocortisone does not improve hemodynamic status.

CCM 2012 (14)

INTERSEPT Enteral nutrition with eicosapentaenoic acid/γ-linolenic acid in early sepsis may ↓ organ dysfunction progression

CC 2011 (15)

SOAP-II Norepinephrine is more effective than dopamine with ↓ arrhythmias and may ↓ mortality in patients with cardiogenic shock

NEJM 2010 (16)

Jones In early sepsis, monitoring lactate clearance is non-inferior to SCVO2

JAMA 2010 (17)

LACTATE Lactate-guided therapy ↓’s hospital mortality AJRCCM 2010 (18)

COIITSS Neither intensive insulin control nor fludrocortisone ↓ mortality in sepsis

JAMA 2010 (19)

VASST Vasopressin + norepinephrine (5 mcg/min) is comparable to raising norepinephrine (5-15 mcg/min).

NEJM 2008 (20)

CORTICUS Hydrocortisone therapy ↓ ’s vasopressor need, but not mortality

NEJM 2008 (21)

CORTISOL In sepsis, adrenal insufficiency is likely if cortisol level is < 10 microg/dl, and unlikely when cosyntropin-stimulated cortisol level is > 44 microg/dl

AJRCCM 2006 (22)

Rivers EGDT ↓ mortality (SCVO >70%, MAP >65, CVP 8-12, Hct >30%).

NEJM 2001 (23)

Annane Hydrocortisone + fludrocortisone x 7 days ↑ survival and ↓ vasopressor duration

JAMA 2002 (24)

PROWESS Xigris (drotrecogin alfa; recombinant activated protein C) ↑ survival in severe sepsis

NEJM 2001 (25)

Levy In septic shock, epinephrine is as effective as dobutamine + norepinephrine, but ↑ gastric mucosal acidosis and risk of mesenteric ischemia, limiting its usefulness as first-line

ICM 1997 (26)

IBUPROFEN In sepsis, ibuprofen ↓’s prostacyclin/thromboxane, fever, tachycardia, oxygen consumption, and lactic acidosis. Does not prevent shock or ARDS and does not ↑ survival

NEJM 1997 (27)

Bone Early, high dose methylprednisolone does not ↓ mortality in septic shock

NEJM 1987 (28)

Cardiology Osawa Goal-directed therapy during cardiac surgery via fluids, inotropes, and blood transfusion ↓30-day complications

CCM 2016 (29)

Cabello There is no conclusive evidence from RCTs to support the routine use of inhaled oxygen in patients with acute MI.

CDSR 2013 (30)

TTM After cardiac arrest with ROSC, no difference between TH at 36° C versus 33° C

NEJM 2013 (31)

Goepfert Early goal-directed hemodynamic therapy after cardiac surgery based on CI, stroke volume variation, and optimized global EDVI ↓’s complications and LOS.

Anest 2013 (32)

IABP- SHOCK II In patients with ACS and cardiogenic shock, IABP does not ↑ survival/oxygenation

NEJM 2012 (33)

DOSE In decompensated heart failure, no difference between high-dose (twice previous dose) versus low-dose furosemide or between furosemide bolus versus infusion

NEJM 2011 (34)

CLUE In hypertensive crisis, nicardipine is more likely to achieve the goal BP within 30 min compared to labetalol

CC 2011 (35)

PARTNER In severe, non-operative aortic stenosis, TAVI ↓’s morbidity, mortality, rehospitalization, but ↑ CVA risk

NEJM 2010 (36)

ECLIPSE After cardiac surgery, clevidipine is comparable to nicardipine on blood pressure control, but better than nitroglycerin or sodium nitroprusside. Clevidipine has ↓ mortality than sodium nitroprusside, but not others.

Anesthesia & Analgesia 2008 (37)

TROICA Tenecteplase does not ↓ mortality in out-of-hospital cardiac arrest

NEJM 2008 (38)

Haas In aortic dissection, esmolol is the beta-blocker of choice. Labetolol is an alternative. After adequate beta-blockade, nitroprusside or nicardipine can be added if needed.

Seminars in Dialysis 2006 (39)

ACUITY Bivalirudin is non-inferior to heparin + glycoprotein IIb/IIIa combination for moderate-high risk ACS patients being managed with early invasive strategy.

NEJM 2006 (40)

OASIS Fondaparinux has similar ischemic endpoints to enoxaparin but ↑ catheter clot formation during PCI.

NEJM 2006 (41)

COMMIT Early beta-blocker after acute MI ↓ arrhythmias and reinfarction

Lancet 2005 (42)

ESCAPE PAC’s do not ↓ mortality in decompensated heart failure JAMA 2005 (43)

SCD-HeFT While amiodarone does not ↓ mortality in patients with heart failure (EF <35%), ICD implantation does.

NEJM 2005 (44)

SYNERGY Enoxaparin is not superior to unfractionated heparin in preventing ischemic events in high-risk ACS patients.

JAMA 2004 (45)

dIVC Changes in IVC diameter by 18% during respiration is an accurate predictor of fluid responsiveness in sepsis

ICM 2004 (46)

EPHESUS Eplerenone ↓’s morbidity and mortality after STEMI with left ventricular dysfunction and heart failure.

NEJM 2003 (47)

MAPPET-3 Alteplase, with unfractionated heparin, in submassive PE is better than heparin alone

NEJM 2002 (48)

MADIT-II ICD can ↓ mortality in patients with prior MI and ejection fraction <30%

NEJM 2002 (49)

Bernard Therapeutic hypothermia (TH) after VF arrest with coma ↓’s mortality

NEJM 2002 (50)

VMAC In acutely decompensated CHF, nesiritide ↑ hemodynamic function (not mortality) + dyspnea more effectively than IV nitroglycerin or placebo, but ↓’s renal function

JAMA 2001 (51)

CURE In UA/NSTEMI, clopidogrel ↓’s morality, MI, or CVA and should be started after CABG for 30 days to 1 year.

NEJM 2001 (52)

TACTICS In UA/NSTEMI, early invasive (<48h after presentation) therapy ↓ mortality, MI, and rehospitalization at 6 months.

NEJM 2001 (53)

SHOCK Emergent PCI after cardiogenic shock with STEMI, LBBB, or posterior infarctions with anterior ST depressions ↓ ’s mortality at 6 mo (not 30 days)

NEJM 1999 (54)

MUSST ICD without antiarrhythmic drugs can ↓ mortality in high-risk patients with coronary disease.

NEJM 1999 (55)

MADIT-I In patients with prior MI, LV dysfunction and risk of ventricular tachyarrhythmia, ICD ↑’s survival

NEJM 1996 (56)

Stiell High dose (0.7mg) epinephrine, as opposed to low dose (0.1mg), does not improve neurologic or cardiac outcome

NEJM 1992 (57)

Pulmonary/ Mechanical Ventilation

Pirrone In morbidly obese patients, a recruitment maneuver followed by PEEP titration improves lung volumes and oxygenation

CCM 2016 (58)

Open Lung Open lung approach in ARDS improves oxygenation and driving pressor without mortality or MVD

CCM 2016 (59)

Guerin The degree of ARDS does not predict the rate of diffuse alveolar damage after open lung biopsy

ICM 2015 (60)

Corley After cardiac surgery, direct extubation to HFNC in pateints with BMI > 30 does not reduce atelectasis or improve pulmonary function

ICM 2015 (61)

PREOXYFLOW Prior to intubating hypoxemic patients, HFNC does not improve the lowest level of desaturation more than high fraction-inspired oxygen facial mask

ICM 2015 (62)

Muriel Simultaneous use of analgesic and sedatives may be associated with failure of NIPPV, but not when used alone

ICM 2015 (63)

Bajaj NIPPV after planned extubation ↓’s reintubation rate in COPD patients and those at high risk for reintubation, and no difference in mixed medical ICU patients

Heart Lung 2015 (64)

Chacko Cochrane review: No Δ in pressure-control or volume-control ventilation for ARDS or ALI.

CDSR 2015 (65)

FLORALI HFNC oxygen improves survival in patients with nonhypercapnic acute hypoxemic respiratory failure

NEJM 2015 (66)

BiPOP High-flow nasal oxygen, versus BiPAP, did not have JAMA 2015

worsened outcomes in cardiothoracic surgery patients (67)AstraZeneca Rosuvastatin does not improve clinical outcomes in

patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction.

NEJM 2014 (68)

PEITHO In patients with intermediate-risk PE, tenecteplase ↓ hemodynamic instability

NEJM 2014 (69)

HARP-2 Simvastatin does not improve outcomes in ARDS NEJM 2014 (70)

BPAP In acute pulmonary edema, BiPAP (rather than CPAP) ↑’s oxygenation faster, ↓ dyspnea scores, and ↓ need for ICU admission without ↑ risk of MI.

JEM 2014 (71)

Lellouche No recommendation to support the use of heated humidifiers during NIPPV with ICU ventilators

ICM 2014 (72)

PROSEVA Proning for at least 16hrs/day in early ARDS ↓’s mortality.

NEJM 2013 (73)

REDUCE 5 days (rather than 14 days) of glucocorticoid treatment in AECOPD

JAMA 2013 (74)

TracMan In patients on vent > 7 days, early tracheostomy does not ↓ mortality

JAMA 2013 (75)

OSCAR HFOV in ARDS does not ↓ mortality/LOS. Study did not use lung-protective strategies

NEJM 2013 (76)

OSCILLATE HFOV in ARDS ↑’s mortality. Study used lung-protective strategies

NEJM 2013 (77)

Needham Cisatracurium for early ARDS x 48hrs ↓’s mortality/LOS/morbidity without ↑ weakness

CJA 2012 (78)

Mavros There is insufficient evidence to support an association between atelectasis and post-operative fever or even that atelectasis causes fever at all.

CHEST 2011 (79)

MI-E Mechanical insufflation-exsufflation ↓’s reintubation rate and LOS

CC 2012 (80)

ACURASYS Cisatracurium for early ARDS x 48hrs ↓ ’s lung inflammation, overt barotrauma, and mortality

NEJM 2010 (81)

PEEP High vs low PEEP does not ↑ hospital survival, but does ↑ survival in patients with ARDS

JAMA 2010 (82)

Terragni Early tracheostomy (6-8 days) compared to late (13-15 days) did not decrease incidence of VAP

JAMA 2010 (83)

CESAR ↑ survival with ECMO in early ARDS Lancet 2009 (84)

PT-OT Early physical + occupation therapy ↓’s MVD, delirium duration, and ↑’s functional outcome

Lancet 2009 (85)

EXPRESS ↑ PEEP to plateau pressure of 28-30 cm H2O ↑’s recruitment/lung function, ↓ duration of organ failure/MVD without Δ mortality

JAMA 2008 (86)

LUNG OPEN Open-lung approach (low tidal volume, recruitment maneuvers, and high PEEP) ↓’s hypoxemia and use of rescue therapies but does not ↓ mortality/barotrauma

JAMA 2008 (87)

ABC Sedation vacation (SV) + SBT versus SBT alone: SV + SBT has ↓ mortality/MVD

Lancet 2008 (88)

Meduri Prolonged, low dose methylprednisolone in early ARDS ↓’s MVD/ LOS/ mortality. If extubated < 2 weeks, give 15 days of therapy; if > 2 weeks, give 28 days. Meduri also had study (1998) showing ↓ lung injury/ mortality

Chest 2007 (89)

LaSRS In late ARDS (7-28 days after onset), steroids ↓ MVD, but not mortality

NEJM 2006 (90)

Baillard For intubation of hypoxemic patients, preoxygenation with NIPPV is more effective than bag-valve mask

AJRCCM 2006 (91)

PAC PA catheters should not be routinely used for the management of acute lung injury.

NEJM 2006 (92)

PIOPED II The predictive value of CTA is high with a concordant clinical assessment, but low in extreme discordance.

NEJM 2006 (93)

Conservative Conservative fluid management ↑’s lung function and ↓’s MVD without ↑ non-pulmonary-organ failures

NEJM 2006 (94)

Nava NIPPV post-extubation is more effective than standard medical therapy in preventing need for re-intubation

CCM 2005 (95)

Esteban Post-extubation respiratory failure, NIPPV (rather than intubation) ↑’s mortality

NEJM 2004 (96)

Keenan Addition of NIPPV to standard medical therapy post-extubation does not improve outcome (See Bajaj, Nava)

JAMA 2002 (97)

SNIFF In non-obese patients without limited head extension, sniff position is not superior to simple head extension

Anest 2001 (98)

ARDSnet Low VT ↑’s survival (12ml/kg vs 6ml/kg) NEJM. 2000 (99)

SCCOPE Steroids x 2 weeks in AECOPD ↓s treatment failure/LOS. NEJM 1999 (100)

PV-LIMITED In ARDS, limiting peak inspiratory pressure and tidal volume does not ↓ and may ↑ morbidity

NEJM 1998 (101)

Kramer NIPPV for acute respiratory failure ↓ ’s LOS, work of breathing, complications and mortality

AJRCCM 1995 (102)

Brochard NIPPV for AECOPD ↓ ’s need for intubation/ LOS/mortality

NEJM 1995 (103)

Brochard-II Weaning is shorter with less treatment failures using pressure-support versus SIMV or T-piece trials.

AJRCCM 1994 (104)

RSBI RSBI (RR/VT) <100 is the best measure for extubation success/failure

NEJM 1991 (105)

PIOPED Clinical judgment + VQ scan only rules in or out PE in the minority with strong clinical + VQ scan findings.

JAMA 1990 (106)

Steroids High-dose steroids does not affect outcome in patients with ARDS (see Meduri, LaSRS).

NEJM 1987 (107)

Gastro-enterology & Nutrition

IRON IV iron supplementation ↑’s serum ferritin but no effect on transferrin saturation, iron-deficient erythropoiesis, Hb, or pRBC requirement.

CCM 2015 (108)

PermiT Moderate, versus full amount, of nonprotein calories via enteral feeding does not lower mortality

NEJM 2015 (109)

CALORIES No difference between enteral and intravenous nutritional support

NEJM 2014 (110)

VITdAL-ICU High-dose vitamin D3 in patients with vitamin D deficiency does not affect mortality or LOS

JAMA 2014 (111)

Early PN Early TPN in patients unable to feed enterally only ↓ vent days, nothing else

JAMA 2013 (112)

Villanueva In patients with UGIB, restrictive transfusion (Hb 7, rather than 9) ↓ mortality. Excluded ACS, massive bleeding, CVA, trauma, LGIB

NEJM 2013 (113)

EDEN In patients with acute lung injury, trophic is comparable to full enteral feeding

JAMA 2012 (114)

EPaNIC Early TPN ↑’s LOS/infection/healthcare cost NEJM 2011 (115)

TICACOS Nutritional support via repeated indirect calorimetry measurements (vs 25 kcal/kg/day) may ↓ mortality

ICM 2011 (116)

Stapleton Omega-3 fatty acids in fish oil do not ↓ pulmonary or systemic inflammation in acute lung injury

CCM 2011 (117)

Chan High-dose IV omeprazole (80mg bolus then 8mg/h infusion for 72 h) is superior to low-dose in preventing peptic ulcer re-bleeding after endoscopic hemostasis

Br J Surg 2011 (118)

Early TIPS Early TIPS ↓’s mortality and treatment failure in cirrhotics hospitalized for persistent variceal bleeding

NEJM 2010 (119)

White No benefit of early post-pyloric feeding over early gastric feeding for nutrition receipt or complications

CC 2009 (120)

Hsu Nasoduodenal (vs nasogastric) feeding had ↓ VAP, vomiting, and earlier time to nutritional goal

CCM 2009 (121)

Andriulli In UGIB after EGD hemostasis, intravenous PPI is comparable to PPI infusion on re-bleeding risk

AJG 2008 (122)

SIC High-dose sodium-selenite ↓’s mortality rate in patients with severe sepsis or septic shock.

CCM 2007 (123)

IAH/ACS IAH is an intra-abdominal pressure > 12 mmHg while ACS is pressures >20 mmHg with organ failure.

ICM 2007 (124)

Lau In UGIB, PPI infusions ↓ recurrent bleeding after endoscopic treatment

NEJM 2000 (125)

Sort Two doses of concentrated albumin in SBP ↓ mortality and need for RRT

NEJM 1999 (126)

Besson Octreotide to sclerotherapy in GIB with varices ↓’s re-bleeding

NEJM 1995 (127)

Mortensen A urea/creatinine ratio > 100 suggests an upper GIB source rather than lower GIB or renal hypoperfusion

Dan Med Bull 1994 (128)

Renal & Fluids AKIKI A delayed strategy (>72hrs), compared to early RRT, does not improve mortality.

NEJM 2016 (129)

Distelmaier 24-hour urinary output predicts mortality in patients undering ECMO following cardiovascular surgery

CCM 2016 (130)

PRELOAD Volume expansion using preload dependence indices (PPV, PLR) ↓ fluids/pRBC’s without Δ outcome

CC 2015 (131)

RENAL In critically ill patients with low caloric intake receiving RRT, greater caloric intake does not improve outcomes

CC 2014 (132)

CONVINT No difference between CRRT and IHD in regards to mortality, RRT days, MVD, LOS, or vasopressor days

CC 2014 (133)

CRISTAL Colloids vs crystalloids: Colloids have ↓ pressor need/vent days/90-day mortality (data is conflicting)

JAMA 2013 (134)

CHEST HES vs saline: no Δ mortality, but HES had ↑ RRT and need for blood

NEJM 2012 (135)

6S HES vs LR: HES has ↑ mortality and ↑ need for RRT NEJM 2012 (136)

CVP CVP correlates poorly with volume responsiveness, and its application to bedside management is uncertain

CCM 2013 (137)

VASST-IVF Positive fluid balance increases mortality risk in septic shock. CVP unreliably gauges fluid balance >12hrs.

CCM 2011 (138)

PLR PLR-induced changes in cardiac output can reliably predict fluid responsiveness regardless of ventilation mode and cardiac rhythm

ICM 2010 (139)

RRT High intensity CVVHDF (40 ml/kg/hr) is not better than low (25 ml/kg/hr).

NEJM 2009 (140)

Furosemide Furosemide after hemofiltration in acute kidney failure ↑’s diuresis + sodium excretion but not renal recovery

CCM 2009 (141)

DELTAPP Minimizing PPV by volume loading during high-risk surgery improves postoperative outcome and ↓ LOS.

CC 2007 (142)

SAFE-TBI ↑ mortality with albumin versus resuscitation with saline in traumatic brain injury patients

NEJM 2007 (143)

FACTT Conservative (net equal) fluids is no different than liberal (net positive) for ARDS

NEJM 2006 (144)

HEMODIAFE Almost all patients with acute renal failure and multi-organ failure can be treated with IHD rather than CRRT

Lancet 2006 (145)

SALT Tolvaptan ↑’s serum sodium at day 4 and 30 in patients with euvolemic or hypervolemic hyponatremia

NEJM 2006 (146)

PAC-Man No clear benefit in managing critically ill patients with a PAC

Lancet 2005 (147)

SAFE No difference in albumin or NS in 28-day mortality NEJM 2004 (148)

FPACSG PAC does not significantly affect mortality and morbidity in patients with shock, ARDS, or both

JAMA 2003 (149)

Phu Venovenous hemofiltration is superior to peritoneal dialysis for infection-associated acute renal failure

NEJM 2002 (150)

ANZICS Abandon “renal-dose dopamine”, it does not ↓ mortality/RRT/LOS

Lancet 2000 (151)

Ronco Increasing the CRRT ultrafiltration rate ↑’s survival and should be prescribed at least 35 mL/h/kg

Lancet 2000 (152)

NeurologyCarrasco In nonintubated patients, dexmedetomidine may have a

better effectiveness, safey, and cost-benefit than haloperidol for agitation due to delirium

CCM 2016 (153)

Al-Qadheeb Scheduled, low-dose haloperidol does not decrease delirium in mechanically ventilated critically ill patients

CCM 2016 (154)

Eurotherm In TBI patients with increased ICP, therapeutic hypothermia did not improve outcomes

NEJM 2015 (155)

FAST-MAG In patients with CVA, prehospital magnesium did not improve disability outcomes at 90 days

NEJM 2015 (156)

REVASCAT In patients with anterior circulation CVA who can be treated within 8 hours of symptoms, stent retriever thrombectomy ↓’s disability.

NEJM 2015 (157)

Swift Prime In patients receiving IV t-PA for acute CVA, thrombectomy with stent retriever within 6 hours improves functionality

NEJM 2015 (158)

Extend-IA In patients with ischemic CVA, early thrombectomy with stent retriever (vs alteplase alone) improved outcome

NEJM 2015 (159)

ESCAPE Rapid endovascular treatment improves outcomes and decreases mortality in patients with ischemic CVA

NEJM 2015 (160)

MR CLEAN In acute ischemic CVA due to proximal intracranial occlusion, intra-arterial treatment within 6 hours ↑’s function, without Δ mortality/bleeding

NEJM 2014 (161)

Prasad Cochrane Review: For status epilepticus, IV lorazepam is superior to diazepam or phenytoin.

CDSR 2013 (162)

CATIS Aggressive BP control does not ↓ mortality in ischemic CVA after tPA

JAMA 2014 (163)

Mueller Dex for severe alcohol withdrawal ↑symptom control and ↓ short-term lorazepam exposure.

CCM 2014 (164)

PAD Protocol-directed management of PAD ↓’s LOS, ventilator days, and mortality.

JCC 2013 (165)

Hope-ICU Haloperidol does not Δ duration of delirium and should be reserved for short-term management of agitation

LRM 2013 (166)

Synergasia Vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in post-resuscitation shock had better neurologic recovery than epinephrine/saline placebo

JAMA 2013 (167)

SLEAP In protocolized sedated patients, SV does not improve outcomes, but instead ↑’s opioid and/or benzodiazepine requirements

JAMA 2012 (168)

Methadone Replacing fentanyl infusion with enteral methadone ↓’s the weaning time from mechanical ventilation

CC 2012 (169)

MIDEX Dex is equivalent to midazolam in sedation with ↓ ICU delirium/ventilator days

JAMA. 2012 (170)

PRODEX Propofol is comparable to dex in sedation/ventilator days/LOS

JAMA 2012 (170)

DECRA Traumatic brain injury with ICP (>20), decompressive craniectomy ↓’s ICP/ LOS but has poor outcomes

NEJM 2011 (171)

Kamel Hypertonic saline is more effective than mannitol for the treatment of elevated intracranial pressure

CCM 2011 (172)

Devlin Quetiapine in addition to haloperidol ↓’s ICU delirium CCM 2010 (173)

StrØm Little to no sedation reduces ventilator days and LOS, but increases ICU delirium

Lancet 2010 (174)

INTERACT Early intensive blood pressure control (systolic of 140 mmHg within 1 h) ↓’s hematoma growth over 72 hours in intracerebral hemorrhage.

Stroke 2010 (175)

UltiSAFE In short term ventilation, remifentanil improves sedation/agitation, ↓ weaning time, MVD and LOS

ICM 2009 (176)

Reade In intubated, agitated, delirious patients, dex (rather than Haldol) allowed for ↓ sedation, LOS, MVD

CC 2009 (177)

ECASS III In patients with ischemic CVA presenting within 3 - 4.5 hrs, alteplase ↑’s outcome

NEJM 2008 (178)

FAST Recombinant factor VIIa does not ↓ mortality in spontaneous ICH

NEJM 2008 (179)

MENDS Dex versus lorazepam: Dex has ↑ coma-free days but ↑bradycardia

JAMA 2007 (180)

CVA In CVA without thrombolytic therapy, initiate antihypertensive treatment only when systolic pressure exceeds 220 mmHg or diastolic >120 mmHg

Circulation 2007 (181)

Gold Escalating diazepam + phenobarbital ↓’s need for vent in patients with DTs

CCM 2007 (182)

REMIFENT Compared with midazolam/fentanyl, a remifentanil- propofol regimen ↓’s MVD and LOS

CC 2006 (183)

Pandhari-pande

Lorazepam ↑’s risk of delirium (midazolam as well, but not statistically significant)

Anest 2006 (184)

CRASH Corticosteroids should not be used for cerebral edema due to trauma or stroke.

Lancet 2005 (185)

Tempkin No benefit of valproate (rather than phenytoin) for prevention of early seizures or treatment of late seizures

Journal of Neurosurgery 1999 (186)

VA Status EpilepticusStudy

In status epilepticus, lorazepam (0.1mg/kg) is superior to phenytoin (18 mg/kg). Lorazepam is equivalent to phenobarbital or phenytoin/diazepam combination

NEJM 1998 (187)

Cook In mechanically ventilated patients, ranitidine had ↓ GIB compared to sucralfate

NEJM 1998 (188)

CAST In ischemic CVA, aspirin within 48hrs ↓’s mortality and recurrent ischemic stroke

Lancet 1997 (189)

Bracken Acute spinal cord injury > 3 hours = methylpred x 24 hours; 3-8 hours = methylpred x 48 hours

JAMA 1997 (190)

Tempkin In patients with severe head injury, phenytoin ↓’s seizures in first 7 days

NEJM 1990 (191)

Allen Nimodipine for SAH ↓’s mortality and neurologic deficits NEJM 1983 (192)

Infectious Diseases

Damas Cochrane Review: Subglottic secretion suctioning ↓’s VAP CCM 2015 (193)

Sehgal Mycobacterium w, an immunomodulator, can ↓ MVD, LOS, incidence of nosocomial infection, and SOFA score

JCC 2015 (194)

Noto Daily chlorhexidine bathing does not ↓ HAI (CLABSI, CAUTI, VAP, or CDI) and is not recommended

JAMA 2015 (195)

HEAT Early use of acetaminophen to treat fever in patients with suspected fever did not improve ICU-free days

NEJM 2015 (196)

STOP-IT Intra-abdominal infections after source control, short course antibiotics (4 days) were similar to long course (8 days)

NEJM 2015 (197)

SDD SDD and SOD are associated with ↓ levels of antibiotic resistance and no Δ mortality. SDD has ↓ rectal carriage of resistant Gram-negative bacteria and bacteremia.

JAMA 2014 (198)

Sood The presence of septic acute kidney injury varies significantly based on the infection site, not the organism

ICM 2014 (199)

AZUREA Antibiotic de-escalation resulted in prolonged LOS and increased risk of superinfection, without mortality

ICM 2014 (200)

ProGUARD Procalcitonin algorithm using 0.1ng/ml cut-off does not achieve 25% reduction in antibiotic duration.

AJRCCM 2014 (201)

AZUREA De-escalation of antibiotics (rather than continuation of empiric therapy) ↑’s LOS but no Δ mortality (patients were unbalanced, raising concerns about the results)

ICM 2014 (202)

Copper Copper alloy surfaces ↓ hospital-acquired infections and/or colonization.

ICHE 2013 (203)

CAP Steroids Review of 8 RCTs show adjuvant steroid therapy for CAP can ↓ LOS but not mortality

J Hosp Med 2013 (204)

BUGG Wearing gowns and gloves for all ICU patients does not ↓ acquisition of MRSA or VRE.

JAMA 2013 (205)

COPPER ICU rooms with copper allow surfaces have ↓ HAI and/or colonization with MRSA or VRE

ICHE 2013 (206)

Dulhunty Continuous infusion of beta-lactam antibiotics achieves ↑ plasma concentrations and clinical cure in sepsis

CID 2013 (207)

Wunderink Linezolid has ↑ cure rate & ↓ nephrotoxicity than vancomycin for MRSA pneumonia, but no Δ mortality. Controversial topic

CID 2012 (208)

Timsit Chlorhexidine-gel-impregnated dressing ↓’s CLABSI. Highly adhesive dressing ↑’s catheter colonization

AJRCCM 2012 (209)

AgTive Silver-nanoparticle-impregnated central venous catheters JHM 2012

do not ↓ colonization, CLABSI, mortality (201)Lorente Manual tooth brushing compared to chlorhexidine oral

care does not help to prevent VAPEJCMID 2012 (211)

FACE Antipyretics independently ↑ 28-day mortality for septic patients (but not for non-septic patients

CC 2012 (212)

Scawn In HAI of unknown origin, 2 days of empiric antibiotics is as safe as 7 days

HTA 2012 (213)

MRSA Individual allocation to MRSA screening, isolation precautions, and decontamination vs standard precautions does not ↓ MRSA acquisition

ICHE 2012 (214)

PRORATA Procalcitonin ↓’s antibiotics, but had no effect on patient outcome

Lancet 2010 (215)

NASCENT Silver-coated endotracheal tube can ↓ VAP without affecting mortality, LOS, or MVD

JAMA 2008 (216)

Palmer Aerosolized antibiotics ↓ VAP, bacterial resistance, systemic antibiotic use, and facilitate weaning

CCM 2008 (217)

VAP therapy VAP with low-risk for resistant bacteria can be treated with monotherapy. For high-risk resistant bacteria, combination therapy may have better outcomes.

CCM 2008 (218)

Lodise Beta-lactam + macrolide combination therapy is superior to quinolone monotherapy in severe CAP

AAC 2007 (219)

Diagnose VAP Getting BAL with quantitative culture vs endotracheal aspiration with non-quantitative cultures have similar clinical outcomes and similar overall use of antibiotics

NEJM 2006 (220)

Kumar Mortality ↑ each hour without antibiotics CCM 2006 (221)

Steroids Meningitis

Steroids with 1st dose of antibiotics in community-acquired bacterial meningitis ↓’s morbidity/mortality

LID 2004 (222)

Paul Addition of an aminoglycoside to beta lactams for the treatment of sepsis is discouraged

Br Med J 2004 (223)

Walsh Empiric caspofungin is as effective and better tolerated than liposomal amphotericin B for neutropenic fever

NEJM 2004 (224)

Shrobik Olanzapine is as effective as haloperidol in delirious critical care patients and is a safe alternative

ICM 2004 (225)

Luna Serial clinical pulmonary infection scores can help assess VAP resolution, prognosis, and therapy duration

CCM 2003 (226)

Chastre 8-days of antibiotics for VAP unless it’s a non-lactose fermenting GNR

JAMA 2003 (227)

PNEUMA With the exception of nonfermenting Gram-negative bacilli, 8 days of therapy is comparable to 15 for VAP

JAMA 2003 (228)

De Gans Dexamethasone for adult Streptococcus pneumoniae meningitis

NEJM 2002 (229)

GIMEMA No improvement in outcome when adding amikacin to piperacillin-tazobactam for febrile neutropenia

CID 2001 (230)

Kress Sedation vacations ↓ VAP NEJM 2000 (231)

Drakulovic Semi-recumbent positions ↓ VAP Lancet 1999 (232)

Bozzette Add steroids to patients with PJP and respiratory failure JID 1990 (233)

HematologyRECESS After cardiac surgery, transfusion of rec cells stored for <10

days was no superior to red cells stored for >21 daysNEJM 2015 (234)

Beitland Low molecular weight heparin reduces the risk of DVT more ICM 2015

than unfractionated heparin, but had no difference in pulmonary embolism, major bleeding or mortality

(235)

TITRE2 After cardiac surgery, a restrictive transfusion threshold (<7.5 g/dL) was not superior to a liberal threshold (<9)

NEJM 2015 (236)

ABLE Transfusion of fresh red cells (<8 days storage) did not ↓mortality as compared with standard storage red cells

NEJM 2015 (237)

FFP-Worth No benefit of FFP across a range of indications (liver disease, warfarin reversal in cardiac surgery, TTP, plasmapheresis, burns, shock, or head injury)

Transfusion 2012 (238)

PROTECT Dalteparin is comparable (LOS/mortality) to unfractionated heparin for DVT prophylaxis

NEJM 2011 (239)

Eerenberg Prothrombin complex concentrate immediately and completely reverses rivaroxaban but not dabigatran

Circulation 2011 (240)

TRACS Restrictive transfusion strategy (Hb >8 g/dL; Hct >24%) rather than liberal does not ↑ mortality

JAMA 2010 (241)

CRASH 2 Tranexamic acid ↓’s mortality in trauma patients with significant hemorrhage

Lancet 2010 (242)

Koch In patients undergoing cardiac surgery, transfusion of pRBC stored > 2 weeks ↑’s postoperative complications (MVD, sepsis) and ↓’s short and long-term survival

NEJM 2008 (243)

Borgman Massive transfusion protocols (>10 pRBC units/day) should utilize a 1:1 ratio of plasma:pRBC

J Trauma 2007 (244)

Netzer Transfusion of RBCs in patients with acute lung injury is associated with increased in-hospital mortality

Chest 2007 (245)

EPO Epoetin alfa does not ↓ pRBC requirement in critically ill, but it may ↓mortality in patients with trauma.

NEJM 2007 (246)

Bussel Eltrombopag ↑’s platelet counts in patients with relapsed or refractory ITP

NEJM 2007 (247)

Shorr Transfusions of pRBC ↑ risk of ICU-acquired bloodstream infection.

Chest 2005 (248)

TRICC With the exception of AMI, conservative pRBC transfusion (goal Hb of 7-9 gm/dL) is as effective as liberal (goal Hb 10-12 gm/dL) and does not ↑ mortality

NEJM 1999 (249)

Apharesis Plasma exchange is more effective than plasma infusion in the treatment of thrombotic thrombocytopenic purpura.

NEJM 1991 (250)

Endocrine

CGAO-REA Tight computerized glucose control (vs conventional) does not ↓ mortality and ↑’s severe hypoglycemia

ICM 2014 (251)

Qaseem ACP recommends not using intensive insulin therapy, but rather to target glucose of 140 to 200 mg/dL

AIM 2011 (252)

NICE-SUGAR Intensive insulin control ↑s mortality. Aim for <180 mg/dl rather than 81-108 mg/dl

NEJM 2009 (253)

VISEP Like NICE-SUGAR, intensive insulin therapy ↑’s hypoglycemia without ↓ in mortality Pentastarch ↑’s renal failure and mortality.

NEJM 2008 (254)

Leuven II Intensive insulin therapy does not ↓ mortality (unlike Leuven I, which showed that it does)

NEJM 2006 (255)

Other Moitra In elderly patients, increased LOS is associated with a higher 1-year mortality

CCM 2016 (256)

3SITES Subclavian-vein catheterization was associated with a lower risk of bloodstream infection and symptomatic thrombosis, but higher risk of

NEJM 2015 (257)

pneumothorax than jugular or femoral veinNRT No statistical benefit from nicotine replacement therapy

on sedation/analgesia, MVD, or LOSResp Care 2013 (258)

CIREA1 No benefit of IPC + GCS over GCS alone on thrombotic event prevention in patients at high-risk of bleeding

ICM 2013 (259)

Heard In acute acetaminophen toxicity with known duration, the Rumack-Matthew nomogram determines the need for IV or oral N-acetylcysteine (NAC) therapy

NEJM 2008 (260)

A-line Heparinized solution for arterial catheter maintenance does not ↑ functionality/duration, but does ↑ aPTT

ICM 2008 (261)

Activated Charcoal

In poisoning/overdose, activated charcoal within first hour is recommended despite lack of proven benefit

Clin Toxicol 2005 (262)

Gastric Lavage

In poisoning/overdose, there is no definite indication for gastric lavage due to lack of confirmed benefit

JTCT 2004 (263)

Cathartics In poisoning/overdose, there is no definite indication for cathartics due to lack of confirmed benefit

JTCT 2004 (264)

Ipecac Syrup In poisoning/overdose, induced emesis with ipecac is not recommended

JTCT 2004 (265)

Daly NAC is recommended in serum acetaminophen level > 10 mg/L or aspartate aminotransferase > 50 IU/L.

AEM 2004 (266)

Index: ↑ – increases; ↓ – decreases; AAC – Antimicrobial Agents & Chemotherapy; ACS – acute coronary syndrome; ACP – American College of Physicians; AECOPD – acute exacerbation of chronic obstructive pulmonary disease; AEM – Annals of Emergency Medicine; AIM – Annals of Internal Medicine; AJG – American Journal of Gastroenterology; AJRCCM – American Journal of Respiratory and Critical Care Medicine; Anest – Anesthesiology; aPTT - activated partial thromboplastin time; ARDS – acute respiratory distress syndrome; BAL – bronchoalveolar lavage; BiPAP – bilevel positive airway pressure; CABG – coronary artery bypass grafting; CAP – community-acquired pneumonia; CAUTI – catheter-associated urinary tract infection; CC – Critical Care; CCM – critical care medicine; CDI – Clostridium difficile infection; CDSR – Cochrane Database of Systematic Reviews; CI – cardiac index; CID - Clinical Infectious Diseases; CJA – Canadian Journal of Anesthesia; CLABSI – central-line associated bloodstream infection; CVA – cerebrovascular accident; CPAP – continuous positive pressure ventilation; CRRT – continuous renal replacement therapy; CVC – central venous catheter; CVP – central venous pressure; CVVHDF – continuous veno-venous hemodialysis filtration; Dex – Dexmedetomidine; ECMO – extracorporeal membrane oxygenation; EDVI – End-diastolic volume index; EF – Ejection fraction; EGD – Esophagogastroduodenoscopy; EGDT – Early goal-directed therapy; EJCMID – European Journal of Clinical Microbiology and Infectious Diseases; FFP – fresh frozen plasma; GCS – graduated compression stockings; GIB – gastrointestinal bleeding; Hb – hemoglobin (gm/dL); Hct – hematocrit; HES - Hydroxyethyl starch; HFNC – High flow nasal cannula; HFO – high-frequency oscillatory ventilation; HTA – Health Technology Assessment; IABP – intra-aortic balloon pump; ICD - implantable cardioverter defibrillators; ICHE – Infection Control and Hospital Epidemiology; ICP – intracranial pressure; IHD – intermittent hemodialysis; ITP – idiopathic thrombocytopenic purpura; IPC – intermittent pneumatic compression; IV – intravenous; JAMA – Journal of the American Medical Association; JCC – Journal of Critical Care; JEM – Journal of Emergency Medicine; JID – Journal of Infectious Diseases; JTCT – Journal of Toxicology, Clinical Toxicology; LID – Lancet Infectious Disease; LBBB – left bundle branch block; LOS – length of stay; LR – lactated ringers; LRM – Lancet Respiratory Medicine; MAP – mean arterial pressure; Methylpred – methylprednisolone; MI – myocardial infarction; MVD – mechanical ventilation days; NEJM – New England Journal of Medicine; NIPPV – non-invasive positive pressure ventilation; NS – normal saline; NSTEMI – non-ST-elevation myocardial infarction; PAC – pulmonary artery catheter; PE – pulmonary embolism; PEEP – positive end-expiratory pressure; PJP – Pneumocystis jiroveci pneumonia; PPI – proton pump inhibitor;

PLR – passive leg raising; PPV – pulse pressure variation; pRBC – packed red blood cells; RCT – randomized controlled trial; RR – respiratory rate; RSBI – rapid shallow breathing index; ROSC – return of spontaneous circulation; RRT – renal replacement therapy; SIMV – Synchronized intermittent mandatory ventilation; SBP – spontaneous bacterial peritonitis; SCVO2 – central venous oxygen saturation; SDD – Selective decontamination of the digestive tract; SOD –selective oropharyngeal decontamination; SOFA – Sequential Organ Failure Assessment; STEMI – ST-elevation myocardial infarction; SV – sedation vacation; TAVI - transcatheter aortic-valve implantation; TIPS - transjugular intrahepatic portosystemic shunt; TH – therapeutic hypothermia; TPN – total parenteral nutrition; UA – unstable angina; UGIB – upper gastrointestinal bleeding; Vent – ventilator; VQ – ventilation/perfusion; VT – Tidal volume.

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