1. Sepsis Don’t be afraid…well actually you should be
David Kovaleski MD FACP FCCP FASN
Intensivist
Respiratory Care Medical Director
Regional Health Inc.
Associate Professor of Medicine
Chief, Critical Care Medicine
Internal Medicine, Nephrology, Critical Care
Sanford School of Medicine
University of South Dakota

2. No Conflicts

3. Keep the Big Picture In Mind

4. Outline What is it? Where have we been… Where are we at…
A little of why we do what we do…
Where are we going…

6. 750,000 cases documented in US annually
2% of patients admitted to the hospital
10% of ICU admissions
19 million cases estimated worldwide per year
Adhikari, Lancet 2010
Incidence increased
Aging population
Drug resistant pathogens
Immunosuppressive drugs
Mortality rates 10-50%
Glen Frey

7. Glen Frey

8. Costs the health-care system nearly 17 billion annually

9. Community and Health Care Causes
Pneumonia most common cause, half
Intraabdominal and urinary sources
Blood cultures positive in only 1/3

10. So…What Is Sepsis?

11. Sepsis Definitions

12. Definitions
A continuum of severity describing the host systemic inflammatory response
Stress that this is a spectrum of syndromes from SIRS progressing to Septic Shock, importance of identifying which step in this spectrum a patient is in to predict outcomes as well as decide on therapies.

13. Terminology Systemic Inflammatory Response Syndrome (SIRS) Sepsis
Temp > 38 or < 36
HR > 90
RR > 20 or PaCO2 < 32
WBC > 12 or < 4 or Bands > 10%
Sepsis
The systemic inflammatory response to infection.
Severe Sepsis
Organ dysfunction secondary to Sepsis.
e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy.
Septic Shock
Hypotension secondary to Sepsis that is resistant to adequate fluid administration and associated with hypoperfusion.
TWO out of four criteria
acute change from baseline
Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101(6), 1644–1655.

14. Lactate As a screen of severity As a marker for goodness
Doesn’t mean an elevated lactate means someone is septic!
For the decision of severity after you determine someone is septic

15. Lactate
Evidence is clear that Lactate levels are predictive of death and MODS
Clearance of lactate is associated with improved survival
Algorithms of care based on lactate clearance appear to work as well or better than other approaches.
Jones AE, Shapiro NI, Trzeciak S, et al. Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial. JAMA: The Journal of the American Medical Association 2010;303(8):739–46.
Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open- label, randomized controlled trial. American Journal of Respiratory and Critical Care Medicine 2010;182(6):752–61.

22. Protocolized Care for Early Septic Shock (ProCESS)
Australasian Resuscitation in Sepsis Evaluation (ARISE)
Protocolized Management of Sepsis (ProMISe)
All used same criteria as Rivers
Powered to detect a 6-8% absolute mortality reduction

25. Identify

29. Definitions Early Sepsis Sepsis Septic Shock
Infection and Bacteremia
Sepsis
Life threatening organ dysfunction
Bacteremia
Septic Shock
Sepsis plus MAP < 65, Lactate greater than 2
Multiple Organ Dysfunction Syndrome

30. Risk Factors ICU Admission Bacteremia Advanced age (> 65)
Immunosuppression
Diabetes and cancer
Community acquired pneumonia
Previous hospitalizations

32. Blinky Light Syndrome

33. What’s the point?
Why do we monitor?

34. The Point is NOT… What is the perfect PAOP or EDVI…
What cardiac output is best for survival…
What SVR is optimal…

35. Bob

36. The Point
Is tissue oxygen delivery sufficient to meet cellular oxygen demands? DO2 = VO2

37. Failure Means… Cellular ischemia Bacterial translocation Sepsis
Worsening shock
Organ Dysfunction
Multiple system organ failure
Death

38. Does the Perfect Monitor Exist?
Are they just random number generators?

39. Principles of Monitoring
Devices don’t save lives!
Outcomes coupled with treatment
Behavior must be changed
Data must be accurate
Clinician has to know how to apply data
Non-invasiveness is not the only goal…
Use the right tool

40. Principles of Monitoring
Monitoring requirements will change
Every patient will have different goals
Don’t rely on one variable
High CO and high SvO2 not always best goals
CO is estimated not measured
Continuous measurement is preferable

41. Definitions Oxygen delivery: DO2 Oxygen consumption: VO2 Oxygen demand
Amount of oxygen pumped to the tissues by the heart
DO2=CO x [(1.39 x Hb x SaO2)+(0.003 x PaO2)]
Oxygen consumption: VO2
Oxygen demand
Amount of oxygen required by the tissues to function aerobically
May exceed both oxygen delivery and consumption

42. Assessing O2 Transport Four Questions
Does oxygen delivery meet the patients needs?
Is cardiac output adequate for consumption?
Is oxygen consumption adequate for demand?
Is the patient’s hypoxemia due to a pulmonary problem or to a low flow state?

43. Oxygen Transport Balance
If oxygen delivery and oxygen consumption are balanced:
“Supply” equals “demand”
The cellular requirements of the body are met
Normal metabolic processes proceed uninhibited
Anaerobic metabolism is minimized

44. Oxygen Transport Balance
If cellular demand exceeds delivery, shock is present
Cellular oxygen is deficient
Energy is produced by anaerobic metabolism with lactic acid as a byproduct
Lactate cannot be reutilized and accumulates:
Metabolic acidosis
Cellular injury
Cellular death

45. Oxygen Transport Balance
Oxygen consumption may just meet demand
Requires high extraction from blood
Places patient at risk for rapid decompensation
Very little physiologic reserve is present
Organs with high baseline oxygen extraction are at a high risk for ischemia

46. Oxygen Transport Balance
Patient survival is improved by optimizing oxygen delivery to ensure that
Oxygen demand is met at baseline
There is adequate physiologic oxygen reserve
to cope with acute increases in oxygen
demand

47. Tools of the Trade Pulmonary Artery Catheter Pulse Waveform Analysis
Flotrac, PiCCO, LiDCO, etc
CO2 Rebreathing
Endotracheal Cardiac Output monitoring
Ultrasound
Esophageal
Transthoracic

48. History Time Out…

49. Wener Forsmann

50. History Time Out…

51. PA Catheter “Gold Standard” for hemodynamic monitoring
Intermittent thermodilution
CO calculated by thermodilution
Measures
CVP
PA pressure
SVR
SvO2
Cardiac filling pressure

52. PA Catheter
Studies
No evidence of increased survival when used for fluid management
So…
No outcome benefit
Extremely invasive
Advanced training for placement
Incorrect parameter interpretation
Still useful
RV CO
PA pressures
SvO2
Cardiogenic shock

53. Esophageal Doppler

54. Less-Invasive Hemodynamic Monitoring

55. History Time Out…

56. Pulse Waveform Analysis

57. Pulse Waveform Analysis
How do they work
Devices
FLOTRAC/Vigileo (Edwards)
FloTrac is the transducer, Vigileo is the monitor
PiCCO (Pulsion)
LiDCO (Lidco)
Other: PRAM, Nexfin, MostCare
Accuracy, limitations
Clinical use

58. Pulse Waveform Analysis
Continuous hemodynamic monitoring
Continuous stroke volume (SV) and cardiac output (CO) by arterial waveform analysis
Continuous preload assessment and fluid responsiveness by pulse pressure variation (PPV) or stroke volume variation (SVV)
Global end diastolic volume (GED) and extravascular lung water (ELW) by transpulmonary thermodilution

59. Pulse Waveform Analysis
How do they work? CO output from arterial waveform?
Arterial waveform
Generated by ejection of blood from LV followed by peripheral runoff
Summation of direct wave and reflected wave
Depends on vascular bed
Compliance
resistance

60. Pulse Waveform Analysis
Heart rate and rhythm
Vasomotor tone
Arterial compliance
Resistance
Static pressures
SAP, DAP, MAP, PP
Dynamic pressures
Over time with resp variation
PPV, SVV, SPV

61. Pulse Waveform Analysis
CO=SV x HR
HR: count pulse rate from arterial waveform
SV: calculated from arterial waveform
PP and area under systolic is proportional to LV SV
Depends on vascular bed properties
Different algorithms used by each

62. Magnitude of cyclic changes correlates with LV preload and degree of fluid responsiveness
PPV of 13% and SVV of 10% discriminates between responders and non-responders
Responder? CO increase 15% with 500 ml fluid bolus

63. Are they any good?
Literature showing PPV, SVV, or SPV are highly predictive for volume responsiveness
Validated in
Positive pressure ventilation
Paralysis/heavy sedation
Regular rhythm
Unreliable with tidal volumes less then 8 ml/kg
Significant variability when compared to PAC CO
In hemodynamic instability, altered vascular tone, poor correlation

64. Limitations Depends on quality of arterial waveform signal
Depends on vascular tone
Unreliable in dysrhythmias,
Mechanical cardiac assist devices
Aortic regurgitation
Validated only in patients with adequate Vt

65. When assessing reliability
Accuracy of measurements compared to the reference standard
Ability to track SV and CO accurately and reproducibly after an intervention
Latter the most important

66. In evaluating monitors
Evaluate new against gold standard
Bland-Altman: assess two methods of clinical measurement
Plot bias against mean CO and determine limits of agreement (LOA)
Calculate mean percentage of error
Clinically acceptable if less than 30%

67. Bioimpedance vs Bioreactance

68. History Time Out…

69. ECHO Advantages Speed: Assessment of all chambers Done within minutes
Anatomic breadth: valves, pericardium, pleural effusion
Noninvasive
Intuitive: structure and function assessed at the same time
Diastolic dysfunction, acute RHF, hyperdynamic obstruction can be assessed

70. Parasternal Long Axis

71. Parasternal Short Axis

72. Apical 4-Chamber

73. Subcostal View

74. IVC

75. Fluids

77. What do we do for the typical ICU problem?

78. One size fits all intervention! How convenient!

80. PA Cath story: still useful in some cases

83. What’s In It And Why Does It Even Matter?
Lactated Ringers
Normal Saline
Plasmalyte
½ NS
Etc
Sodium 204 example

84. How Much Sodium is in 1 liter of Normal Saline?
Explain it simply analogy

86. Conclusions? Early identification still paramount Just enough fluid
Early antibiotics
Need a process, but jury is still out on which one

87. Path To Insanity Emcrit.org Podcast #105

88. Path To Insanity Novice: Just trying not to look stupid
Advanced Beginner: Start problem solving, narrow focus
Competent: Start trouble shooting, proficient, learn from others mistakes
Most level off here
Does not equal excellence
Proficient: gain reflection, don’t need someone to tell you where you went wrong, you can do innately, learn from others mistakes
Expert: True intuition, no longer helped by rules but are hindered by them, capable of invention on the fly

89. “As long as you have a brain, you’re not a slave to the numbers.”

90. Thank You