Update in Critical Care Medicine Michael A. Gropper, MD, PhD Professor and Executive Vice Chair Department of Anesthesia and Perioperative Care Director, Critical Care Medicine UCSF
Disclosure None
Update in Critical Care ICU Staffing Update on glycemic control Sedation Shock resuscitation: fluids Mechanical ventilation Early Mobilization
Retrospective cohort study of 65,762 patients in 49 ICU s in 25 hospitals participating in the APACHE clinical information system 2009 2010 Measured the impact of nighttime intensivist staffing on outcomes in low and high intensity staffed ICU s N Engl J Med 2012;366:2093 101
Nighttime Intensivist Staffing N Engl J Med 2012;366:2093 101
Nighttime Intensivist Staffing N Engl J Med 2012;366:2093 101
Glycemic Control: The end of a sad story?
Intensive Insulin Therapy in Critically Ill Patients (van den Berghe et al. N Eng J Med 2001) Randomization Blood glucose level when insulin infusion was started Infusion adjusted to maintain blood glucose Conventional >215 mg/dl 180 to 200 mg/dl (10.0 and 11.1 mmol/l) Intensive >110 mg/dl 80 to 110 mg/dl (4.4 to 6.1 mmol/l)
Benefits of intensive insulin therapy compared to conventional insulin therapy 0-10 -20-30 -40-50 -60 In hospital mortality Blood stream infections ARF requiring dialysis Red cell transfusions Critical illness polyneuropathy van den Berghe et al. N Eng J Med 2001
Randomized, prospective trial of 6104 patients Glucose targets of 81-108 mg/dl versus 180 mg/dl or less Primary endpoint was death within 90 days of randomization NEJM 2009
NICE SUGAR NEJM 2009
NICE SUGAR: Outcomes NEJM 2009
Glycemic Control: A Sour Taste Analysis of the NICE SUGAR database Follow up data on 6026 patients N Engl J Med 2012;367:1108 18.
<70 <40
Odds Ratio for Death
Which drug should we use for sedation of critically ill patients, and how should we use it?
Systematic review of RCT s and observational studies with metaanalysis Sepsis patients who received etomidate for intubation Measured mortality and adrenal insusfficiency Crit Care Med 2012;40:2945 2953
Mortality after Etomidate All cause mortality in all studies All cause mortality in RCT s Crit Care Med 2012;40:2945 2953
Adrenal Insufficiency All studies RCT s Crit Care Med 2012;40:2945 2953
Two randomized, prospective trials: MIDEX: Dexmedetomidine vs Midazolam PRODEX: Dexmedetomidine vs Propofol Measured time at target sedation, duration of mechanical ventilation, LOS, ability to communicate JAMA. 2012;307(11):1151 1160
Dexmedetomidine vs Midazolam and Propofol JAMA. 2012;307(11):1151 1160 MIDEX PRODEX
Ability to Communicate JAMA. 2012;307(11):1151 1160
Randomized, prospective trial in 128 patients Daily sedation interruption Restart at 50% dose Duration of MV decreased from 7.3 to 4.9 days NEJM 2000
Protocolized Sedation + Daily Wake Up Randomized, prospective trial with 430 patients Randomized to protocolized sedation vs protocolized sedation plus daily wake up Measured time to extubation, ICU and hospital LOS, delirium, workloadtotal drug doses Mehta et al, JAMA. 2012;308(19):
Time to Extubation Mehta et al, JAMA. 2012;308(19):
Sedation Interruption: Outcomes
Total Sedative Doses
Which fluids should we use for resuscitation of critically ill patients?
Which Fluid Should We Use for Resuscitation? Randomized, prospective trial of 4% albumin versus normal saline for fluid resuscitation 6997 patients randomized Primary outcome was 28 day mortality NEJM 2004
Albumin vs Saline SAFE Study: NEJM, 2004 Prospective, randomized study of 6997 patients Objective need (one): tachycardia, hypotension, low PCWP, low Urine Output Normal saline vs 4% albumin for resuscitation All other management the same Primary outcome: 28d mortality Secondary outcomes: Survival time, new organ failures, duration of mechanical ventilation, ICU LOS
Albumin vs Saline SAFE Study: NEJM, 2004
Crystalloid vs Colloid Resuscitation Randomized, 2x2 trial of IIT and Pentastarch Resuscitation Stopped at interim analysis because of increased mortality in IIT group Brunkhorst, NEJM 2008
Crystalloid vs Colloid Resuscitation Brunkhorst, NEJM 2008
Crystalloid vs Colloid Resuscitation Randomized, 2x2 trial of IIT and Pentastarch Resuscitation Stopped at interim analysis because of increased mortality in IIT group N Engl J Med 2008;358:125 39
Crystalloid vs Colloid Resuscitation N Engl J Med 2008;358:125 39
Multicenter, parallel group, randomized blinded trial 804 patients with severe sepsis Randomized to 6% HES 130/0.42 or Ringer s acetate Primary outcome was death or end stage kidney failure (RIFLE E) at 90d N Engl J Med 2012;367:124 34.
N Engl J Med 2012;367:124 34.
Crystalloid vs Colloid N Engl J Med 2012;367:124 34.
Prospective, open label, sequential period pilot study 760 patients in control period, then 773 in intervention period Control: Standard IV fluids (0.9% saline, 4% albumin, 4% gelatin) Intervention: Low Cl: Plasmalyte, Hartmann s, chloride poor albumin Measured: Cr increase in ICU, Incidence of AKI, LOS, mortality JAMA. 2012;308(15):1566 1572
Chloride and Renal Failure Chloride administration is ubiquitous Many solutions are hyper physiological Exacerbate hyperchloremia Metabolic acidosis Renal vasoconstriction Decreased GFR Decreased urine output during surgery JAMA. 2012;308(15):1566 1572
Comparison of Fluids JAMA. 2012;308(15):1566 1572
Incidence of AKI JAMA. 2012;308(15):1566 1572
Development of AKI 2009 (Low Cl ) 2008 (Hi Cl ) JAMA. 2012;308(15):1566 1572
Need for RRT in ICU JAMA. 2012;308(15):1566 1572
Shock Resuscitation: Update
JAMA. 2010;303(8):739 746 Multicenter, randomized trial of 300 patients with severe sepsis or septic shock ScvO2 group was resuscitated to normalize central venous pressure, mean arterial pressure, and ScvO2 of at least 70% lactate clearance group was resuscitated to normalize central venous pressure, mean arterial pressure, and lactate clearance of at least 10% The study protocol was continued until all goals were achieved or for up to 6 hours.
Oxygen Delivery and Consumption
Patients well matched. JAMA. 2010;303(8):739 746
JAMA. 2010;303(8):739 746
Lactate Clearance vs ScvO 2 JAMA. 2010;303(8):739 746
Multicenter, randomized trial including 1679 patients in septic shock Randomized to dopamine or norepinephrine If still hypotensive after 20 mcg/kg/min dopamine or 0.19 mcg/kg/min norepi, open label norepi, epi, or vasopressin could be added. Primary endpoint was 28 day mortality
Dopamine vs Norepinephrine N Engl J Med 2010;362:779 89.
Dopamine vs Norepinephrine N Engl J Med 2010;362:779 89.
Adverse Events Dopamine Norepi N Engl J Med 2010;362:779 89.
Mechanical Ventilation: What s New?
Barotrauma in ALI/ARDS
Pressure-volume relationship appropriate V t V excessive V t protective V t P flex P aw
Consensus conference to update 1994 definitions Instead of ALI/ARDS, now defines 3 categories of ARDS No more PA pressures Standard settings for PaO 2 /FiO 2 measurement JAMA. 2012;307(23):2526 2533
Berlin Definition of ARDS JAMA, June 20, 2012 Vol 307, No. 23
Ventilator Free Days NEJM 2000
Mortality Prior to Hospital Discharge P=0.0054 6 ml/kg 12 ml/kg NEJM 2000
Lellouche et al, Anesthesiology, 2012 Prospective observational trial of 3,434 consecutive adults undergoing cardiac surgery Three tidal volume groups defined: Low: below 10 ml/kg of predicted body weight Traditional: 10-12 ml/kg of predicted body weight High: more than 12 ml/kg of predicted body weight Assessed risk factors for: Prolonged mechanical ventilation Hemodynamic instability Renal failure Prolonged ICU stay
Lellouche et al, Anesthesiology, 2012
Lellouche et al, Anesthesiology, 2012 Distribution of Vt by weight Tidal volume/actual weight versus BMI
Risk Factors for Multi-Organ Failure Lellouche et al, Anesthesiology, 2012
Meta analysis of 20 articles with 2822 patients JAMA. 2012;308(16):1651 1659
Protective Ventilation: Demographics JAMA. 2012;308(16):1651 1659
Protective Ventilation: Outcomes Lung Injury Mortality JAMA. 2012;308(16):1651 1659
Protective Ventilation and Complications Pulmonary Infection Atelectasis JAMA. 2012;308(16):1651 1659
Long term consequences of critical illness: Prevention
Prospective cohort of 1194 patients with severe sepsis Comparison group of 5574 hospitalizations without severe sepsis Long term follow up with measurement of functional status JAMA. 2010;304(16):1787 1794
Long term Consequences of Severe Sepsis JAMA. 2010;304(16):1787 1794
Functional Status After Sepsis JAMA. 2010;304(16):1787 1794
Early Mobilization Critically ill patients rapidly develop weakness Diaphragm atrophy Protein calorie malnutrition Difficulty weaning from mechanical ventilation Pressure ulcers Deep venous thrombosis Long term functional status implications Lipshutz and Gropper, Anesthesiology, 2012
Risk Factors Lipshutz and Gropper, Anesthesiology, 2012
Lipshutz and Gropper, Anesthesiology, 2012
Mobility Score 5 4 3 2 1 Treatment Number vs. Mobility Score: Dedicated Therapist Series1 Poly. (Series1) 0 Eval 5 Treatment Number Treatment Number vs. Mobility Score: No Dedicated Therapist Mobility Score 4 3 2 1 Series1 Poly. (Series1) 0 Eval 1 Treatment Number
Conclusions Nighttime intensivists don t add value to highlystaffed ICU s Glycemic control is dangerous Dexmedetomidine may be helpful Daily wake ups may not be necessary with targeted sedation Synthetic colloids should be avoided Consider switching to lower chloride containing resuscitation fluids Lactate clearance is a good guide for resuscitation Get your patients out of bed!!