SEPSIS Trevor Langhan October 4 th, 2007 Thanks to Dr. Jason Lord FRCPC CCM.
Transcript of SEPSIS Trevor Langhan October 4 th, 2007 Thanks to Dr. Jason Lord FRCPC CCM.
SEPSIS
Trevor LanghanOctober 4th, 2007Thanks to Dr. Jason Lord FRCPC CCM
M & M Case Presentation
59 year old male 5 day Hx generalized abdo pain and
diarhea with rigors PMHx
Liver abscess 1999 Shoulder abscess 1990 EtOH abuse Pancreatitis DM II HTN
Case Presentation
Meds: Insulin, Metoprolol, Lipitor Sept 25
23:13 Temp 40.2 HR 132 BP 140/90 RR 32 Sat 88% RA Confused, flushed, dry mucous
membranes
Case Presentation
P/E: Abdomen:
generalized tenderness but no peritoneal signs, no Murphy’s,
Chest:clear bilat
CVS:HS normal, No murmurs
Remainder of exam non-contributory
Case Presentation
Labs WBC 4.1 (3.2 neuts, 0.2 bands) Hgb 142 Platelets 110 Cr 116 AP 206, TBili 26, ALT 56, GGT/Lipase N
ABG 7.52/29/49/24 Lactate 1.1
Case Presentation
ECG Sinus Tach CXR #1 clear Urine small blood nil else CT abdo:
thickened dilated GB wall with pericolic fluid
No stones, no CBD thickening c/w acute cholecystitis suggest U/S for
confirmation
Resuscitation MeasuresTime Therapy
0010 Bolus 1 L NS
0054 Bolus 1 L NS
0130 NS @ 150 cc/hr
0152 Bolus 1 L NS
0235 NS @ 150 cc/hr
0500 Bolus 1 L NS
0600 Bolus 250 cc Pentaspan
0620 Bolus 250 cc Pentaspan
Resuscitation MeasuresTime Therapy
0810 Blood c/s drawn (9 hours in)
0825 ICU consult for CT
0930 Abx given (10 hours in)
1030 U/S abd
1200 CT abd
1230 Lasix 40 mg IV
1400 ICU MD
1425 Request bed ICU
1545 Transfer to ICU
1710 Perc cholecystostomy
Vital SignsTime Temp HR BP Sats
0145 41 114 94/56 94% 4L
0235 38.8 100 100/50
0410 38.2 100 70/42 92% 4L
0615 104 84/60
0715 99 82/51 95% 4L
0825 96 87/56 90% 5L
1050 91 96/60 90% 5L
1210 62%
1425 98 105/58 90% NRB
Interesting quotes on chart
04:00 “patient looks relatively well despite BP”
05:45 “patient likely septic but no obvious focus”
05:45 “if no response to fluids consider CVP and
pressors if patient symptomatic” 07:30
“consult ICU to see if patient safe for CT abd”
Sepsis
Why are we talking about this AGAIN!
Sepsis and spectrum of infectious disease presentations to ED poorly recognized
Mild under-resuscitation – perk up pt well enough for ward followed by ICU admit 1-2 days later
Case One
42 year old woman c/o epigastric pain Onset 2 hours after eating ROS
Mildly obese Nil else
Case One
PMHx Gall stones
Meds and Allergies none
Case One
Vitals HR 110 RR 16 BP 118/70 Sat 96% room air Temp 37.6 C Glucose 9.0
Physical Tender epigastrum, no peritonitis
Case One
Labs: Hgb 140 Platelets 289 WBC 14.2 Lytes, creatinine normal Lipase 2029 LFTs normal
CT abdomen Acute pancreatitis
Case One
IV fluid 500 cc NS bolus 125 cc NS per hour maintenance
Analgesia Morphine prn Gravol prn
Plan NPO, Admit to general surgery
Diagnosis?
Case Two
14 year old male c/o sore throat x 3 days Still going to school and playing golf PMHx: nil Meds/Allergies: nil
Case Two
HR 95 BP 110/70 RR 16 Temp 38.4 Sat 99% Glucose 6.0 Throat Swab done by GP yesterday
+ve for GAS
Case Two
Plan Oral antibiotics Increase oral fluids RTER prn
Diagnosis?
Case Three
32 year old woman 3 day Hx productive cough Chills, feeling unwell PMHx: nil Meds: none Allergies: none
Case Three
HR: 110 RR: 22 O2 Sat: 91% BP: 140/76 Temp: 38.6 C
ABC’s OK O2, IV, monitor applied CBC, lytes, BUN, Cr, cultures sent CXR ordered
Are there any other investigations?
What would you order next?
Two of:
•HR > 90
•RR > 30
•T > 38 or < 36
•WBC > 12 or <4
Mortality: 10%
The Septic Spectrum
SIRS
SIRS + Infection
SEPSIS
• Lactic Acidosis
• Oliguria
• Altered mental status
Mortality: 16%
The Septic Spectrum
SEPSIS
SEPSIS + Organ Dysfunction
SEVERE SEPSIS
• Severe Sepsis +/- hypotension despite
adequate fluid resuscitation
Mortality: 46%
The Septic Spectrum
SEVERE SEPSIS
SEPTIC SHOCK
Mortality: 46%
The Septic Spectrum
SEVERE SEPSIS
SEPTIC SHOCK
SEPSIS
SIRS
Mortality: 10%
Mortality: 16%
Mortality: 30%
The Septic Spectrum
EARLY Goal Directed Therapy can decrease mortality
SEPTIC SHOCK
Partially RCT Early (< 6 hours) goal directed
protocol vs. standard of care Inclusion:
Systolic BP < 90 after 30cc/kg bolus 2 of 4 SIRS criteria
Outcomes: Inhospital mortality
A priori Power Calculation
500cc boluses as needed to get CVP 8-12 sBP<90 pressors Central venous O2 sats measured
<70% pRBC to achieve HCT >.30 Dobutamine if optimized HCT and MVO2 sats
<70% ETI if not already done if unable to achieve
HD goals
Results: N=263
Case Three
HR: 110 RR: 22 O2 Sat: 91% BP: 140/76 Temp: 38.6 C
Trauma: The Golden hour
What would you do next?
Septic Shock: Early Goal Directed Therapy
Myocardial Infarct: Door-to-needle times
Successful resuscitation requires quick intervention
Lactate If not available…venous or arterial
blood gas Why?
You can’t act early if you don’t know the clock is ticking!
What would you order next?
HR: 145 RR: 28 BP: 85/35
2 litres of NS
O2Sat: 92% on FiO2 100%
CXR shows RLL consolidation Lactate 6.4
Septic ShockSeptic Shock
Patient’s condition is worsening…
What kind of shock is this?
Hypovolemic
Vasodilatory Cardiogenic Obstructive
√√√
Hinsaw/Cox 1972
What kind of shock is this?
Hypovolemic Vasodilatory Cardiogenic Obstructive
CVP 8-12
MAP > 65
ScvO2 >70%
The goals of “Early Goal Directed Therapy” address the 3 types of shock present in a
septic patient
Why are septic patients hypovolemic?
Hypovolemic ShockGoal: CVP 8-12
Hypovolemic ShockGoal: CVP 8-12
Why are septic patients hypovolemic? 3rd spacing Diaphoresis Increased losses (vomiting, diarrhea, etc)
Main reason is not because of less fluid, but because of a larger container…
…Venodilation
Different fluids distribute to different places
Doesn’t matter what – just give enough!Carlson RW. Fluid Resus. in Circulatory ShockCrit. Care Clin. 1993;9:313.
Distributive Shock Goal: MAP > 65
Once ‘tank is full’ CVP 8-12 mmHg Need to increase vascular tone Vasoactive agents
Vasopressors Inotropes
Vasoactive Agents
Adrenergic Receptors
Alpha adrenergic receptors: vascular walls - peripheral vasoconstriction
Beta adrenergic receptors Beta 1: myocardium - increase inotropy (force
ofcontraction) and chronotropy (heart rate)
Beta 2: vascular walls - peripheral vasodilatation
lungs - bronchial smooth muscle relaxation
Dopamine receptors renal and splanchnic arteries - vasodilatation
and inc blood flow
Norephinephrine (Levophed)
Acts mainly on Alpha1 receptors (small clinical effect on Beta receptors)
Inc BP through peripheral perfusion slight tachycardia
Inc afterload by vasoconstriction Use cautiously in cardiogenic shock
Dec perfusion to kidneys and peripheries “Leave ‘em Dead”
Martin, et al., Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? , Chest 1993.
Norepinephrine or Dopamine in septic shock? DBRCT dopamine 10-25mcg/k/m levo 0.5-5.0 mcg/k/min N=32 Outcomes: HD endpoints after fluid
resuscitation
Martin, et al., Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? , Chest 1993.
Successful achievement of endpoints more common with levo than dop
91% vs 31%, p=<0.0001. 10/11 unable to achieve HD endpoints
with dopamine achieved EP with levo
Marik, et al., JAMA. (272), 1994.
RCT N=20 with MAP<60 but still with CI>3.2 to levo or dope
Intervention: titrating pressor to MAP>75 Outcomes:
HD Endpoints. Survival not reported. Results
Norepi increases MAP by increasing SVRI not CI Dop by increasing CI. Also sig increased
splanchnic O2 requirements (?increased risk of ischemic gut)
Cochrane Review:(updated) Feb. 11, 2005. RCTs1. Levo vs Dop (3 studies, N=62)
RR death 0.88 (0.57,1.36)
2. Levo + dob vs epi (N=52) RR death 0.98 (0.57,1.67)
3. Vasopressin vs placebo (N=58) RR death 1.04 (0.06,19.33)
Vasopressin??
RCT levo-resistant septic shock N=48. All pts NE>0.5 mcg/k/m Vaso 4U/hr Cross-over permitted at 24hrs Endpoints: primarily HD
Take Home: Vasopressin when added to levo:
improves myocardial performance No demonstrable benefit on:
kidneys or mortality Less pro-arrhythmic than levo
stat significant decrease in arrhythmias
Case Four
You have just intubated a 71 yr male with a COPD exacerbation.
Post intubation, the nurses report his BP as 60 systolic.
Resuscitating with fluids What are likely etiologies
of the new shock state?
Ventilator malfunction
Natural Hx of disease
Side effect of medication
Loss of vascular tone
Tension Pneumo
Decrease Preload & CO
Case Four
Loss of vascular tone with sedation for intubation
Worsening vasodilation Resuscitating with fluids What agent might you use
peripherally to increase the BP?
Ephedrine
Direct Beta1 and Beta2 receptor Indirect Alpha1
through noradrenaline release Inc BP and HR, some
bronchodilation
Ephedrine
Preparation: 5% solution (50mg in 1cc ampule) Dilute 1/10 with NS 1cc (5 mg) IV increments
Duration of action – 5-15 min Ideal for pregnancy as does not
reduce placental blood flow
Phenylephrine
Pure direct-acting Alpha1 agonist Inc BP via peripheral
vasoconstriction Associated with reflex dec HR Dosing – 10 mg/cc vial
Mix 10 mg (1cc) in 100cc NS – provides concentration of 100 mcg/cc
Administer as 1-2cc increments IV Infusion 20-50 mcg/min
Epinephrine
Direct Alpha1, Beta1 and Beta2 receptors
Inc HR, force of contraction, CO Increase SBP
may dec DBP via vasodilation in skeletal muscle beds
Bronchodilation through Beta2 response
What kind of shock is this?
Hypovolemic Vasodilatory Cardiogenic Obstructive
CVP 8-12
MAP > 65
ScvO2 >70%
The goals of “Early Goal Directed Therapy” address the 3 types of shock present in a
septic patient
Cardiogenic – ScvO2 > 70%
ScvO2 – Used as a marker of success of O2
delivery need a central line preferred superior vena cava
True or False ScvO2 is measured in the coronary
sinus
Cardiogenic – ScvO2 > 70% 51 year male New diagnosis pneumonia HR 120, RR 24, Sat 91%, BP 100/60 Lactate is normal What do you expect his ScvO2 to
be?
Cardiogenic – ScvO2 > 70% Early in sepsis spectrum heart is
hyperdynamic ScvO2 may even be high/normal
Severe sepsis and septic shock Toxins and hostile environment
lead to cardiac dysfunction Pump begins to fail Poor delivery of O2 to periphery
Dobutamine
Targets: Beta1 and Beta2 receptors
minimal action on Alpha1
Increases CO: Inotropy Chronotropy decreased afterload
Dosing 2-20 mcg/kg/min
Cardiogenic – ScvO2 > 70% Oxygen delivery Carrying capacity of O2 formula:
CaO2 = (SaO2 x Hb x 1.34) + .003(PaO2)
Can impact the formula by providing more carrying substrate
Dissolved gas is negligible in this setting
Packed RBCs
Increase the O2 carrying capacity Intravascular volume expansion 1U PRBC
increase Hgb by 10 x 10E9/L Availability:
O neg. – Immediate Type specific blood – 15 min Type & Cross Matched – 45 min.
What might supercede EGDT? Give the bug juice! Order it STAT Get the team calling pharmacy early Close the loop Double check that the patient
received it Can be on going while placing
central line and getting fluids
Early Antibiotics
JAMA, 1999
The Importance of Antibiotics
Delay in antibiotics increases mortality: 9.9% in the first hour Mean of 7.6%/hour for the first 6 hours
Kumar et al. Critical Care Medicine 2006. 34(6): 1589-1596.
• Delay in antibiotics increases mortality:– 9.9% in the first hour– Mean of 7.6%/hour for the first 6 hours
Risk of in-hospital mortality increases 9% for every hour of delay in administration of the correct antibiotic
The Importance of Antibiotics
Garnacho-Montero et al. Critical Care 2006. 10:R111
• Delay in antibiotics increases mortality:– 9.9% in the first hour– Mean of 7.6%/hour for the first 6 hours
• Risk of in-hospital mortality increases 9% for every hour of delay in administration of the correct antibiotic
Garnacho-Montero et al. Critical Care 2006. 10:R111
The Importance of Antibiotics
Rapid, broad spectrum ABx given IV as soon as possible
Antibiotic Selection Chest
Levo & ceftriaxone Azithro & Ceftriaxone
Belly Pip Tazo or AGF
Urine Cefriaxone or Gent
Skin Ancef Think about Vanco
Head Ceftriazone, Vaco &
Dex
Anti-Microbials:Critical Care Medicine, 2004.
Where did the patient come from? Home, nursing home or in-hospital (?MRSA risk) Good evidence that poor choice Abx has a bad
outcome
Source control if possible Ie. can a surgeon help? Do they have a central line or cath?
Make sure you investigate all possible sources prior to Abx if at all possible
Case Six (a)
78 year lady Urosepsis PMHx: DM, atrial fibrillation Meds: coumadin, metformin,
glyburide HR 110, BP 90/50, RR 28, Sat 91%
Case Six(a) Has received
EGDT ETT Pressors Antibiotics
Despite your care HR 110, BP 85/50, RR 26, Sat 90%
Anything else before she goes to ICU?
Case Six (b)
66 year old lady PMHx rheumatoid arthritis, OA, DM Meds: Tylenol prn, insulin,
prednisone Productive cough and progressive
respiratory distress New infiltrate on CXR Dx: pneumonia with sepsis
Case Six (b) HR 100, RR 30, Sat 90%, BP 90/60 Lactate: 5.0 Treated with
EGDTFluids (CVP approx 12 cmH2O)ETTVasopressorsTransfused blood to get Hgb > 100
Antibiotics
Case Six (b) Despite all that care HR 110, RR 24, BP 80/40, Sat 90%
She will be going to ICU Anything else to do before she
goes?
Should she get the cream or the clear?
Steroids in Septic Shock: 2 Groups of Patients
1. Relative adrenal insufficiency2. Previous steroid therapy
Supraphysiologic doses clearly shown to increase mortality
DBPRCT, n = 300 Inclusion:
septic shock on pressors SBP <90 signs end-organ hypoperfusion
Excluded: pregnant, MI, PE, CA, AIDS NB no etomidate within prev 6hrs.
Outcomes: mortality (ICU, Hosp, 28 day)
Annane, D. et al., Effect of Treatment With Low Doses of Hydrocortisine and Fludrocortisone on Mortality in Patients With Septic Shock. JAMA, 2002. vol 288 (7).
Stratified by response to corticotropin stimulation test
Short Corticotropin Test250mcg IV ACTHcortisol immediately before then at 30 and
60mins Individual pt response based on highest
post-ACTH compared with pre-ACTH Intervention
50mg solu-cortef IV Q6h and 50mcg Florinef OD
Annane, D. et al., Effect of Treatment With Low Doses of Hydrocortisine and Fludrocortisone on Mortality in Patients With Septic Shock. JAMA, 2002. vol 288 (7).
Mortality decreased by 10% in ACTH ‘non-responders’
Annane, D. et al., Effect of Treatment With Low Doses of Hydrocortisine and Fludrocortisone on Mortality in Patients With Septic Shock. JAMA, 2002. vol 288 (7).
Steroids in Septic Shock
For pts naïve to steroids: Once therapy optimized And the patient is failing pressors
And circulating the drain: Draw random serum cortisol
At least > 6hrs post-etomidate Can give dex since wont interfere
with cortisol response
Case Seven
40 year old female prostitute Florid PID with pelvic abscesses and
extension into peritoneal cavity You have secured the airway The vasoactive agents are working
their magic Fluid and bug juice have been given Gyne will take to the OR
What Vent Setting Doctor?
ARDS
Non cardiogenic pulmonary edema Nonspecific response of the lung to
insult Defined as respiratory failure:
Requirement for mechanical ventilation PaO2/FiO2 ratio < 200
ARDS
Causes: Sepsis and/or
shock Toxic gas/smoke
inhalation Aspiration Pneumonia Drug reaction Trauma
Causes: Transfusion
reaction Burns Pancreatitis Fat/air/amniotic
fluid emboli DIC High altitude
exposure
ARDS
On CXR will see: New, bilateral, diffuse, patchy
pulmonary infiltrates
No clinical evidence of CHF, fluid overload or chronic lung disease Pulm wedge pressure < 18 mmHg
RCT Patients with strictly defined
ARDS** Traditional ventilatory parameters
12cc/kg (predicted ideal wt) Intervention (=low Tv)
6cc/kg , RR variable to achieve near normal pH
Trial stopped at interim analysis
Vent Protocols:
ARR Death 8.8% (2.4,15.3)
NNT = 11 Higher peak plateau
pressures in traditional arm
25 vs 33higher risk of
barotrauma
Ventilation Parameters
Ventilate patient with small tidal volume 6-8 cc/kg
Rate *** bpm required to maintain adequate minute ventilation Often requires sedation and paralysis
Peak pressure goal below 35 cm H20 Mean pressures must account for PEEP
Titrate FiO2 – start 100% but titrate down to prevent alveolar collapse
Case Eight
81 year old male Lobar pneumonia Intubated, fluid replete, pressors
and abx on board Vent set to ARDS protocol ABG – improving lactate, venting
appropriately On gas glucose 18.1 mmol/L
Bacteremic patients Lower rate of mortality
29.5% vs 12.5% ??ARR for all-comers with critical illness
3.4%, NNT = 29 Lower rate of developing sepsis
4.2% vs 7.8%, p=0.003 Reduced frequency of sepsis in all-
comers
Take home points: After everything else has been done
can aim for euglycemia Use cautiously in your optimized
patients NB
Hyperglycemia MIGHT be bad Hypoglycemia IS bad
Case Nine
91 year old lady Multiple co-morbidities Uroseptic in ED Received
EGDT Abx Tight glucose control ARDSNET parameters
Case Nine
91 year old lady Still needing increasing vasoactive
agents to maintain MAP > 55 MSOF – LFTs up, Cr up, no u/o Family asks:
“isn’t there something more you can do?”
“can’t you save my gramma?”
Activated Protein C (aka Xigris) Rationale:
The acute inflammatory response in sepsis is integrally related to endothelial activation and procoagulant state
rhAPC is an endogenous anti-coagulant and potent anti-inflammatory agent
DBPRCT Inclusion:
Severe sepsis or septic shockSick patients (APACHE >25)
all had 1 (most had 2) organs down Exclusion:
Many criteria Outcomes:
Mortality at 28d
Take-Home ICU decision
based on risk of death
Should be aware of the bleeding complications
6 Interventions that Make a Difference1. EGDT
• ARR Mortality 16% NNT 62. Early Abx3. ARDS Net Vent Strategy
• ARR 8.8% NNT 104. Steroids (for Non-Responders)
• ARR 10%, NNT 105. Insulin (tight glucose control)
• ARR 10%, NNT 106. APC (Xigris)
• ARR 6-7%, NNT 16
ED care EGDT
Fluids Pressors Blood
Early Abx Source control
Ventilate with low tidal volumes Euglycemia Consider steroid replacement Think about Xigris
Questions?