sepsis - medicine.uci.edu · host’s systemic inflammatory response syndrome (sirs) to infection....
Post on 23-Mar-2019
217 Views
Preview:
TRANSCRIPT
Sepsis
Fundamentals of Acute Care
Rohit H. Godbole, MD Pulmonary - Critical Care Fellow UC Irvine
Ignaz Semmelweis (1818-1865)
Sepsis History. http://www.sepsis-gesellschaft.de/DSG/Englisch/Disease+pattern+of+Sepsis/Sepsis+History
Objectives
● Understand the definition of sepsis
● Know the presenting signs and symptoms of a septic patient
● Understand the basics of sepsis management including IV fluid support, ino-
pressors, early antibiotics
Importance of Sepsis
● Sepsis syndrome was first described in Ancient Egypt and defined as sepsis by
the Greeks (from the Greek word sipsi for “make rotten”)
● Each year, 31 million people worldwide are treated for sepsis out of which 5.3
million people end up dying
● In the US, it is the most expensive medical condition currently treated with a
cost estimate of $23.7 billion
● 80% of deaths may be prevented with early detection and treatment of sepsis
Sepsis History. http://www.sepsis-gesellschaft.de/DSG/Englisch/Disease+pattern+of+Sepsis/Sepsis+History Fleischman C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, et al. (2016) Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med 193(3): 259-272. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, et al. (2016). The Third International Consensus Definitions for Sepsis and Septic Shock (sepsis-3). JAMA 315(8): 801-810. Torio CM, Andrews RM (2015) National Inpatient Hospital Costs: The Most Expensive Conditions in Payer: HCUP Stateistical Brief#160. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality. Sepsis Alliance. (2016) Sepsis 2016 fact sheet. http://www.sepsisalliance.org/downloads/2016_sepsis_facts_media. pdf
Difficulty Understanding Sepsis
● Syndrome is not well understood
● No specific gold standard diagnostic test
● Definitions and diagnostic criteria continue to evolve
● No universally adopted treatment plan
● Problems with reporting requirements (eg. Core Measures)
● Complicated incentives/disincentives to infections in patients
Surviving Sepsis Campaign
● 1992 - ACCP/SCCM conference proposes definitions for sepsis, severe sepsis, SIRS
● 2001 - expansion of diagnostic criteria for previously defined terms; no change to
prior definition
● 2015 - Sepsis definition changed; SOFA, qSOFA definition proposal
● 2015 - Core Measures implemented by CMS
● 2016 - International Guidelines for Management of Sepsis and Septic Shock
● 2017 - IDSA position paper on not endorsing Surviving Sepsis Guidelines
Sepsis Definition Timeline Hippocrates (460 -
370 BC)
Hugo Schottmüller
(1914)
Sepsis 1 (1992) Sepsis 2 (2001) Sepsis 3 (2016)
Internal rotting or decay
(sipsi in Greek)
Sepsis identified in late
stages of sepsis
“Sepsis is present if a
focus has developed
from which pathogenic
bacteria, constantly or
periodically, invade the
blood stream in such a
way that this causes
subjective and objective
symptoms”
Sepsis results from a
host’s systemic
inflammatory response
syndrome (SIRS) to
infection. Severe sepsis
is sepsis associated
with organ dysfunction,
hypoperfusion, or
hypotension. Septic
shock is sepsis-induced
hypotension persisting
despite adequate fluid
resuscitation.
Keeping definition of
Sepsis 1 but knowing
limitations
Creating diagnostic
criteria
Acknowledging different
stages of sepsis
Sepsis is defined as a
life-threatening organ
dysfunction caused by
a dysregulated host
response to infection.
Septic shock is a
subset of sepsis in
which particularly
profound circulatory,
cellular, and metabolic
abnormalities are
associated with a
greater risk of mortality
than with sepsis alone.
Rittirsch D, Flierl MA, Ward PA. (2008) Harmful Molecular Mechanisms in Sepsis. Nat Rev Immunol 8(10): 776-787. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, et al. (1992) Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis. Chest 101(6):1644-1655.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, et al. (2016). The Third International Consensus Definitions for Sepsis and Septic Shock (sepsis-3). JAMA 315(8): 801-810.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, et al. (2008) Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008. Intensive Care Med 34(1): 17-60.
By 2009, sepsis awareness
campaigns helped achieve a 25%
reduction in mortality!
Core Measures
On October 1st, 2015 Centers
for Medicare and Medicaid
Services required a minimum
set of actions at specific time
interval.
The CMS definitions, the
mandates, and withholding of
payment to hospitals became
problematic.
Defining Sepsis (Sepsis-3)
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host
response to infection.
Septic shock is a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Issues with the publication:
● Only US and European patient populations, does not take into account poor resource countries
● Did not include opinions of ER physicians
Management: Goals and Objectives
● Early Goal Directed Therapy (EGDT) ○ Does it help?
● IV fluids ○ How much volume to give
○ What type of fluid to give
● Ino-pressors ○ Inotropes vs. Vasopressors
● Antibiotics ○ Broad-spectrum
○ Can use procalcitonin to inform antibiotic de-escalation
● Mechanical Ventilation ○ Consider early initiation
Management: EGDT
● Early goal directed therapy
In 2001, Rivers et al published their findings of using protocol-based
management in the care of patients with severe sepsis and septic shock
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77
Management: EGDT
● Early Goal Directed Therapy
Three large trials (ProCESS, ARISE, and ProMISe) were
conducted and none of them showed a difference in
mortality between the EGDT arm and Standard care arms
of their studies… but this was attributed to improved
overall care of sepsis even in control arm from improved
sepsis education
ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for
early septic shock. N Engl J Med 2014; 370:1683.
ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for
patients with early septic shock. N Engl J Med 2014; 371:1496.
Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic
shock. N Engl J Med 2015; 372:1301.
Management: EGDT
● What is early goal directed
therapy? ○ CVP 8 - 12 mmHg
○ MAP ≥ 65 mmg
○ ScVO2 ≥ 70%
○ UOP 0.5 mL/kg/min
Management: EGDT ● 3.4.1 Early Goal Directed Therapy (EGDT) (See also protocol flowchart in Appendix A)
○ Supplemental O2, Mechanical Ventilation, Target SpO2 ≥ 95%
○ Insert CVC for continuous ScvO2 reading (IJ, subclavian okay, NOT femoral)
○ Start IVF boluses in 500 cc increments every 30 minutes until CVP is 8-12 mmHg
○ Insert arterial line
○ If MAP < 65, initiate vasopressors to titrate MAP between 65-90 mmHg
○ If MAP > 90, consider afterload reduction
○ If ScvO2 is < 70% and Hct is < 30%, transfuse PRBCs until Hct is > 30%
○ If ScvO2 < 70%, Hct is > 30%, inotrope such as dobutamine can be started (initial dosing 2.5
ug/kg/min, increasing until ScvO2 > 70%, HR > 120, arrythmias develop or max dose of 20
ug/kg/min is attained)
○ At 6 hours, subject returns to standard care
ProCESS Investigators, Yealy DM, Kellum JA, et al. A
randomized trial of protocol-based care for early septic
shock. N Engl J Med 2014; 370:1683.
Management: Goals and Objectives
● Early Goal Directed Therapy (EGDT) ○ Does it help?
● IV fluids ○ How much volume to give
○ What type of fluid to give
● Ino-pressors ○ Inotropes vs. Vasopressors
● Antibiotics ○ Broad-spectrum
○ Can use procalcitonin to inform antibiotic de-escalation
● Mechanical Ventilation ○ Consider early initiation
Management: IV Fluids
● Where did we get 30 mL/kg? ○ Rivers et al: 4981 +/- 2984 mL
○ ProCESS: 2800 mL
○ ARISE: 2515 +/- 1244 mL (34.9 mL/kg)
○ ProMISe: 2000 mL (median)
Rough math works out to about 30 mL/kg!
* All values are for EGDT group at initial resuscitation 0-6 hours
ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014; 370:1683.
ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371:1496.
Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015; 372:1301.
Management: IV Fluids
● Which type of fluid to use? ○ Balanced crystalloids
ORIGINAL ARTICLE
Balanced Crystalloids versus Saline in Critically Ill Adults
Matthew W. Semler, M.D., Wesley H. Self, M.D., M.P.H., Jonathan P. Wanderer, M.D., Jesse M. Ehrenfeld,
M.D., M.P.H., Li Wang, M.S., Daniel W. Byrne, M.S., Joanna L Stollings, Pharm.D., Avinash B. Kumar,
M.D., Christopher G. Hughes, M.D., Antonio Hernandez, M.D., Oscar D. Guillamondegui, M.D., M.P.H.,
Addison K. May, M.D.,
Management: IV Fluids
● Which type of fluid to use? ○ Balanced crystalloids
● 7942 patients in the balanced-crystalloids group vs. 7860 patients in saline group:
○ 1139 (14.3%) had a major adverse kidney event vs. 1211 of 7860 patients (15.4%) in the saline group
(marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95%
CI, 0.82 to 0.99; P=0.04).
○ Among patients with sepsis, 30-day in-hospital mortality was 25.2% with balanced crystalloids and
29.4% with saline (adjusted odds ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02)
Semler M et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med 2018; 378:829-839
Management: Goals and Objectives
● Early Goal Directed Therapy (EGDT) ○ Does it help?
● IV fluids ○ How much volume to give
○ What type of fluid to give
● Ino-pressors ○ Inotropes vs. Vasopressors
● Antibiotics ○ Broad-spectrum
○ Can use procalcitonin to inform antibiotic de-escalation
● Mechanical Ventilation ○ Consider early initiation
Ino-Pressors ● Inotropic action: Beta receptors
● Vasopressor action: Alpha receptors
Drug Alpha-1 Beta-1 Beta-2 Dopaminergic
Predominant Clinical Effects
(Neosynephrine) Phenylephrine *** 0 0 0 SVR ↑ ↑, CO ↔/↑
(Levophed) Norepinephrine *** ** 0 0 SVR ↑ ↑, CO ↔/↑
(Adrenalin) Epinephrine *** *** ** 0
CO ↑ ↑, SVR ↓ (low dose) SVR/↑ (higher dose)
(Intropin) Dopamine
(mcg/kg/min)
0.5 to 2 0 * 0 ** CO 5 to 10 * ** 0 ** CO ↑, SVR ↑
10 to 20 ** ** 0 ** SVR ↑ ↑
Management: Ino-Pressors
● VASST Trial
Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper J et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008; 358:877-887.
Management: Ino-Pressors
● VASST Trial
There was no difference in primary end-
points of 28-day and 90-day mortality in the
NE vs. V groups, but there were no more
complications either
Management: Ino-Pressors
● VANISH Trial
There was no
difference in primary
end-point (kidney
failure-free days for
first 28 days), but
there was a reduction
seen in the incidence
of RRT in vasopressin
groups
(i.e. using
vasopressin early
may avoid HD)
Management: Goals and Objectives
● Early Goal Directed Therapy (EGDT) ○ Does it help?
● IV fluids ○ How much volume to give
○ What type of fluid to give
● Ino-pressors ○ Inotropes vs. Vasopressors
● Antibiotics ○ Broad-spectrum
○ Can use procalcitonin to inform antibiotic de-escalation
● Mechanical Ventilation ○ Consider early initiation
Antibiotics ● Broad spectrum antibiotic with coverage for the organism that most likely is causing
the suspected sepsis syndrome
● When choosing, consider the following: ○ Patient’s history
○ Comorbidities
○ Immune status
○ Risk of MDRO (eg. nursing homes)
○ Foreign objects (lines, ports, prosthetic materials)
○ Local hospital antibiogram
● Common organisms: E. coli, S. aureus, Klebsiella, S. pneumoniae
Antibiotics ● Common regimen depends on likely organism:
● MRSA
● Vancomycin
● Daptomycin (non-pulmonary)
● Linezolid
● Pseudomonas
● Cephalosporin: Ceftazidime, Cefepime
● Carbapenem: Imipenem, Meropenem
● Beta-Lactam/Beta-Lactamase Inhibitor: Piperacillin-Tazobactam
● Aminoglycoside: Amikacin, Tobramycin, Gentamicin
● Atypicals: Azithromycin
● Anaerobes: Metronidazole, Carbapenems, Piperacillin-Tazobactam
Management: Goals and Objectives
● Early Goal Directed Therapy (EGDT) ○ Does it help?
● IV fluids ○ How much volume to give
○ What type of fluid to give
● Ino-pressors ○ Inotropes vs. Vasopressors
● Antibiotics ○ Broad-spectrum
○ Can use procalcitonin to inform antibiotic de-escalation
● Mechanical Ventilation ○ Consider early initiation
Mechanical Ventilation
● Consider in patients with increasing pressor requirements, worsening metabolic
acidosis and compensatory tachypnea resulting in increased work of breathing
● Consequences of not intubating early: ○ Aspiration
○ Myocardial infarction
○ Respiratory muscle fatigue
○ Higher risk intubation when patient is much more ill
When on rounds...
Previous SIRS criteria (1992):
● Two or more of: Temperature >38°C or <36°C
● Heart rate >90/min
● Respiratory rate >20/min or PaCO2 <32 mm Hg (4.3 kPa)
● White blood cell count >12 000/mm3 or <4000/mm3 or >10% immature bands
qSOFA
● Respiratory Rate ≥ 22
● Altered mentation
● Systolic blood pressure ≤ 100 mmHg
qSOFA is not meant for diagnosis or as a
definition of sepsis… it is a mortality predictor,
but can also be used as a trigger to initiate
further work-up
What to do?
● ASSESS FIRST ○ See the patient
○ Obtain vital signs
○ Draw labs
■ Blood cultures
■ Lactate
■ Procalcitonin
○ Does the patient need other work-up?
■ Eg. imaging
● DISCUSS ○ Call for help
■ Attending, Pulm-CC fellow, other
consultants
■ Upgrade level of care
Case 4
A 47-year-old woman is evaluated in the emergency department for progressive lethargy and confusion. Her husband reports a 3-day history of subjective fever and chills, and the development of right-sided lower back pain during the last 24 hours.
She collapsed without loss of consciousness 4 hours ago after rising from a chair. She has noted blood in the urine for about 6 days, was recently diagnosed with a urinary tract infection, and began treatment with empiric oral cephalexin.
She has a history of kidney stones but no chronic kidney disease, hypertension, or other chronic medical conditions.
Case 4 Urine leukocyte count 103,000/µL (103 x 109/L)
Urine leukocyte esterase positive
Urine nitrites positive
Multiple bacteria are observed on microscopic examination of the urine.
Leukocyte count 23,100/µL (23.1 x 109/L)
Neutrophil count 74% with 15% bands
Blood hemoglobin 8.1 g/dL (81 g/L)
Platelet count 115,000/µL (115 x 109/L)
Lactate 4.9 mEq/L (4.9 mmol/L)
Troponin negative
Central venous pressure 10 mm Hg
Case 4
Based on the laboratory studies, the patient is started on two empiric antibiotics intravenously.
She is given 2L (approximately 30 ml/kg) normal saline during the first 3 hours. Her blood pressure after initial intravenous fluid bolus is 70/35 mm Hg and repeat plasma lactate is 4.7 mEq/L (4.7 mmol/L).
A CT scan of the abdomen is ordered but will not be performed for 60 minutes.
Case 4
According to the referenced guidelines, which of the following is the most appropriate management?
A. Crystalloid infusion and titration for target central venous pressure of 14 mm Hg
B. Dopamine infusion and titration to mean arterial pressure greater than 65 mm Hg
C. Norepinephrine infusion and titration to mean arterial pressure greater than 65 mmHg
D. Transfusion with 2 units of packed red blood cells
Summary
● Understand the definition of sepsis
● Know the presenting signs and symptoms of a septic patient
● Understand the basics of sepsis management including IV fluids, ino-pressors, early
antibiotics, mechanical ventilation
References ● Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, et al. (2016). The Third International Consensus Definitions for Sepsis and Septic Shock (sepsis-3).
JAMA 315(8): 801-810.
● Gary T, Damien M, Yenamandra A. The evolving definition of sepsis. arXiv:1609.07214.
● Fleischman C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, et al. (2016) Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and
Limitations. Am J Respir Crit Care Med 193(3): 259-272
● Torio CM, Andrews RM (2015) National Inpatient Hospital Costs: The Most Expensive Conditions in Payer: HCUP Stateistical Brief#160. Healthcare Cost and Utilization
Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality.
● Sepsis Alliance. (2016) Sepsis 2016 fact sheet. http://www.sepsisalliance.org/downloads/2016_sepsis_facts_media. Pdf.
● Rittirsch D, Flierl MA, Ward PA. (2008) Harmful Molecular Mechanisms in Sepsis. Nat Rev Immunol 8(10): 776-787.
● Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, et al. (1992) Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis. Chest
101(6):1644-1655.
● Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, et al. (2008) Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic
Shock: 2008. Intensive Care Med 34(1): 17-60.
● Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77
● ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014; 370:1683.
● ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;
371:1496.
● Semler M et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med 2018; 378:829-839
● Russell JA et al. Vasopressin versus norepinephrine in patients with septic shock. N Engl J Med 2008; 358:877-887.
● Gordon AC et al. Effect of early vasopressin versus norepinephrine in patients with septic shock. JAMA. 2016;316(5):509-518.
top related