What ICU Evidence Applies to the OR?
Ross Blank, MD
Assistant Professor
Division of Critical Care
Director, Thoracic Anesthesia
What We Do
Anesthesia providers practice intensive care.
• Airway Management• Mechanical Ventilation• Fluid Resuscitation• Vasopressor Support• Antibiotic Management
VENTILATOR MANAGEMENTWhat Works in ARDS?
What is ARDS?
Definition formalized in 1992 American European Consensus Conference
1. Acute onset, bilateral infiltrates on CXR
2. PCWP ≤ 18 mmHg or no clinical evidence of left atrial hypertension
3. PaO2/FiO2 (P/F) Ratio
≤ 300 for ALI
≤ 200 for ARDS
Bernard et al. AJRCCM 1994;149:818-824
What is ARDS? – Berlin Definition
The ARDS Definition Task Force. JAMA 2012;307:2526-2533
Treatments of ARDS
Non-pharmacologicLow tidal volumes
High PEEP
Recruitment maneuvers
Prone positioning
High Frequency Oscillatory Ventilation (HFOV)
Airway Pressure Release Ventilation (APRV)
Conservative fluids
Renal Replacement Therapy
Early enteral feeding
PA Catheter
ECMO
PharmacologicCorticosteroids
Nitric oxide
Alkali Therapy
Neuromuscular blockade
Ketoconazole
Lisofylline
Oxepa
Antioxidants
Neutrophil elastase inhibition
Exogenous surfactant
Liquid ventilation
Inhaled β-agonists
Statins
Treatments of ARDS with Mortality Benefit
Non-pharmacologicLow tidal volumes (ARMA, NEJM 2000)
High PEEP (meta-analysis, JAMA 2010)
Recruitment maneuvers
Prone positioning (NEJM 2013)
High Frequency Oscillatory Ventilation (HFOV)
Airway Pressure Release Ventilation (APRV)
Conservative fluids
Renal Replacement Therapy
Early enteral feeding
PA catheter
ECMO?
PharmacologicCorticosteroids?
Nitric oxide
Alkali Therapy
Neuromuscular blockade (NEJM 2010)
Ketoconazole
Lisofylline
Oxepa?
Antioxidants
Neutrophil elastase inhibition
Exogenous surfactant
Liquid ventilation
Inhaled β-agonists
Statins
ARDSNet ARMA Trial
RCT of 6 mL/kg vs. 12 mL/kg PBW Tidal Volume
Further TV adjustments to maintain PPLAT < 30 cm H2O vs. < 50 cm H2O
Ventilator Mode – Volume Control A/C
PEEP/FiO2 per table in both groups
861 patients
Mortality 31.0% vs. 39.8% (p = 0.007)
NEJM 2000;342:1301-1308
Transpulmonary Pressure (PTP)
Slutsky and Ranieri. NEJM 2013;369:2126-2136
PTP – Talmor Trial
PTP – Talmor Trial• Calculated as difference
between airway pressure and pleural pressure from esophageal balloon
• Measured after end-expiratory and end-inspiratory occlusions
• After RM, adjust PEEP for goal PTP,exp 0-10 cm H2O, decrease TV to keep PTP,insp < 25 cm H2O
• On average, increased PEEP in experimental group (17 vs. 10 cm H2O) associated with increased PO2, improved compliance, lower FiO2, and modest increases in peak, plateau, and mean airway pressures
• Control group generally had negative PTP,exp
Talmor et al. NEJM 2008;359:2095-2104
PTP – Talmor Trial
Static Compliance =
TV/(PPLAT - PEEP)
The observation that PEEP increases were associated with more modest PPLAT increases demonstrates the improvement in compliance
Talmor et al. NEJM 2008;359:2095-2104
Compliance Curve
Blanch et al. Curr Opin Crit Care 2007;13:332-337
Compliance low:Atelectasis, Shunt
Compliance low:OverinflationHigh VD/VTBest Compliance
PTP – Talmor Trial
• Small trial (n = 61)• Single center• Unexpected signal of
decreased 28-day mortality in experimental group
• Interestingly, 3/30 experimental group patients actually had their PEEP lowered based on initial PTP measurements . . . one size does not fit all
• Follow-up, large, multi-center trial ongoing
Talmor et al. NEJM 2008;359:2095-2104
Why is PTP relevant to the OR?
• Elevated pleural pressure is an indicator of decreased chest wall compliance
• We deal with decreased chest wall compliance every day – thoracic/abdominal operations, thoracoscopy, laparoscopy, head-down position, obesity, pregnancy, ascites, effusions, skeletal deformities, etc. etc.
Why is PTP relevant to the OR?
• In general, high airway pressures measured on the ventilator suggest that we may have to lower PEEP and tidal volume to prevent barotrauma and/or lung injury
• In situations of decreased chest wall compliance, higher pressures (both PEEP and PIP) may be necessary to overcome the elevated pleural pressure
A simpler way to set PEEP?
1. Perform RM
2. Decremental PEEP trial while measuring dynamic compliance
3. Identify PEEP associated with highest compliance
4. Repeat RM and set PEEP at or just above PEEP determined above
This PEEP corresponds to CT scan findings just before atelectasis appears . . . in pigs after lung lavage.
Suarez-Sipmann et al. Crit Care Med 2007;35:214-221
A simpler way to set PEEP?
Maisch et al. Anesth Analg 2008;106:175-181
FLUID RESUSCITATIONHow Much? To What End? Which One?
Septic Shock - Early Goal-Directed Therapy
Over 6 hours:
More Fluid (5.0 L vs 3.5 L)
More Blood (64% vs. 19%)
More Dobutamine (14% vs. 1%)
Less Death (30.5% vs 46.5%)
Rivers et al. NEJM 2001;345:1368-1377
Septic Shock – Lactate Clearnace
Jones et al. JAMA 2010;303:739-746
Septic Shock – Lactate Clearnace
Control group – Rivers Protocol
Intervention group – Replace ScvO2 goal with ≥ 10% lactate clearance every 1-2 hours
No differences in ScvO2 levels, length of stay, or mortality
Jones et al. JAMA 2010;303:739-746
Alternatives to Crystalloid - SAFE
NEJM 2004;350:2247-2256
Alternatives to Crystalloid
Albumin
•Human-derived•Expensive•Established indications
•Safe
Hydroxyethyl Starch
•Synthetic•Relatively inexpensive•Widely used
•Safe?
Alternatives to Crystalloid - CHEST
Myburgh et al. NEJM 2012;367:1901-1911
6% HES 130/0.4
Increased rate of renal replacement therapy, no difference in mortality in HES group (n = 6651)
Alternatives to CrystalloidNEJM 2008;358:125-139
NEJM 2012;367:124-134
Crit Care 2012;16:R94
Control = LR
Alternatives to CrystalloidNEJM 2008;358:125-139
NEJM 2012;367:124-134
Crit Care 2012;16:R94
↑ RRT↑ Deathn = 698
↑ RRTn = 537
No differencesn = 196
Control = LR
Alternatives to Crystalloid - CRISTAL
• Multi-center trial conducted in 57 ICUs from 2003-2012• Patients received either all crystalloid or all colloid for resuscitation needs but
specific fluid not specified• No difference in 28-day mortality or need for RRT, decreased 90-day mortality
in colloid group• More ventilator- and vasopressor-free days in colloid group
Annane et al. JAMA 2013;310:1809-1817
What about the control group?
• Retrospective study of 22,851 surgical patients
• 22% incidence of postoperative Cl- > 110 mmol/L
• Hyperchloremic patients developed more renal dysfunction, had longer hospital stays, and demonstrated increased 30-day mortality compared to propensity-matched controls
• “Normal” saline is the only common fluid likely to cause hyperchloremia
McCluskey et al. Anesth Analg 2013;117:412-421
Alternatives to Crystalloid
JAMA 2012;308:1566-1572
Ann Surg 2012;255:821-829
Ann Surg 2014;259:255-262
Crystalloid SolutionsNS LR Plasma-Lyte/
NormosolPlasma
Na+ 154 130 140 136-146
K+ 4 5 3.5-5.0
Ca2+ 3 2.1-2.6
Mg2+ 3 0.6-1.0
Cl- 154 109 98 98-108
HCO3- 22-34
Lactate 28
Acetate 27
Gluconate 23
Osm 308 273 294 280-300
VASOPRESSOR THERAPYWhat is Tangible Bias?
Vasopressor Choice - Phenylephrine
Thiele et al. Anesth Analg 2011;113:284-296Thiele et al. Anesth Analg 2011;113:297-304
Vasopressor Choice - Phenylephrine
“Favoring less important but immediately measurable variables, such as mean arterial blood pressure (MAP), over more important but less measurable variables, such as tissue oxygen delivery (DO2), is the result of “tangible bias,” our tendency to favor what we can see and understand over what we cannot. Despite the practicalities that preclude the routine measurement of regional blood flow, changes in global and regional blood flow should be anticipated any time hemodynamics are manipulated, with the goal being adequate DO2 and nutrients to organs of interest.”
Thiele et al. Anesth Analg 2011;113:284-296
Vasopressor Choice - Phenylephrine• Arterial vasoconstriction increases MAP/SVR/afterload and thus
increases myocardial oxygen demand – most relevant in cases of pre-existing myocardial failure
• Venoconstriction may decrease venous capacitance and initially increase venous return/RV preload but the resulting increase in venous resistance limits sustained increase in venous return/cardiac output
• Likely decreased myocardial, renal, and mesenteric blood flow
• Net effect is an increase in MAP associated with a decrease in cardiac output
Thiele et al. Anesth Analg 2011;113:284-296
Vasopressor Choice – Surviving Sepsis
Dellinger et al. Crit Care Med 2013;41:580-637
Vasopressor Choice – NE vs. Dopa
De Backer et al. NEJM 2010;362:779-789
SOAP II Investigators’ multi-center RCT of norepinephrine vs. dopamine in treatment of shock
No mortality difference but more arrhythmias in dopamine group
Vasopressor Choice – NE vs. Epi
CATS trial of norepinephrine/ dobutamine vs. epinephrine for septic shock pts
No significant mortality difference or increase in adverse advents with epinephrine
Annane et al. Lancet 2007;370:676-684
Vasopressor Choice – NE vs. AVP
Russell et al. NEJM 2008;358:877-887
VASST trial of norepinephrine vs. low-dose vasopressin for septic shock pts
No significant mortality difference or increase in adverse advents with vasopressin
Why not phenylephrine for septic shock?
• No large trial comparing it to first-line therapy i.e. norepinephrine
• Pharmacologic concerns regarding decreased cardiac output
• Only literature reference is a small trial of 32 patients that documented no measurable differences between phenylephrine and norepinephrine in terms of cardiac function and global/regional perfusion
Morelli et al. Crit Care 2008;12:R143
ANTIBIOTIC MANAGEMENTWhere are the RCTs?
Rapid Treatment
• There is already an evidence-based push for early intervention in acute coronary syndromes and strokes
• We have seen that early fluid resuscitation saves lives in septic shock
• Where are the trials of early antibiotics?
Early, Effective Antibiotics
Kumar et al. Crit Care Med 2006;34:1589-1596
Combination Therapy
Kumar et al. Crit Care Med 2010;38:1773-1785
Possible Benefits:– More likely to cover
resistant pathogens– Synergy?– Prevent development
of resistance?
Often advocated for suspected Pseudomonas infections and for neutropenic patients
All SEPTIC SHOCK pts
Classes of Antibiotics
Penicillins (i.e. peni-, ampi-, piperacillin)β-lactam/β-lactamase inhibitors (i.e. amp-
sulbactam, pip-tazobactam)Cephalosporins (i.e. ceftriaxone, cefepime)Carbapenems (i.e. imi-, meropenem)
Aminoglycosides (i.e. genta-, tobramycin)Fluoroquinolones (i.e. levo-, ciprofloxacin)Macrolides (i.e. azithromycin)
CELL WALLACTIVEAGENTS
PROTEIN SYNTHESIS INHIBITORS
Conclusions
• We take care of critically ill patients in the OR
• There is significant overlap between “healthy” outpatients and sick inpatients
Conclusions
• Lung-protective ventilation, alveolar recruitment, goal-directed fluid resuscitation, the dangers of certain fluids, vasopressor/inotrope selection, rational yet aggressive use of antibiotics – these are concepts that we can and should apply in the OR every day
