Transcript Document

Sepsis: An Update on Pathophysiology and
Treatment Approaches
Case Studies: An Overview
Learning objectives
• Review real cases to understand when to use
activated Protein C
• Note important differences between cases that
influence decision to use or not use aPC
• Discuss “red flags” for particular patients that
could make you nervous about using aPC
Starting from common ground…
• Appropriate supportive care
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ABCs
Fluids
Vasopressors/inotropes
Organ support (ventilation, dialysis, etc.)
• Appropriate empiric and adjusted antibiotics
• Source control
• Avoiding delays in diagnosing severe sepsis/septic shock,
providing supportive care
Case #1
26 year old female
Past history of seizure disorder, on phenytoin
Presents with 12 hour history of fever/chills/rigors, lower
abdominal pain, no dysuria, no cough
39.4 degrees C
HR 125, BP 75/40 --> 90/50 after 2L NS
No CV angle tenderness
No other obvious source
Urinalysis
– 5-20 WBC/hpf
– Bacteria seen
Investigations
Laboratory:
– WBC 1.0, 22% bands, Hb normal, plts normal
– LFT’s normal, lytes, amylase normal
– Creat 139
Radiology:
– CXR clear
– CT (contrast) chest & abdomen: free fluid pelvis,
edematous left kidney
Case: Deterioration
Started on empiric antibiotics following cultures
(Cefotaxime, Cipro, Ampicillin, Flagyl)
12hrs later:
– HR to 180, BP 65/P despite ++ fluids
– Shortness of breath, RR 40+
– Hypoxemia, bilateral pulmonary infiltrates
– 7.23/PCO2 33/pO2 100/bic 14 on 80% O2
– Metabolic acidosis, lactate 2.6
– Increased transaminases, decreased urine output
– Increased INR to 2.4
Case
– Intubated, mechanical ventilation, central venous
catheter, arterial catheter, vasopressor
– Blood cultures: Gram negative bacillus 2/2 bottles
– PA catheter
• Cardiac index 2.5L/min/m2
• PCWP 17
– Expected mortality now >40%
• Septic Shock, ARDS
Source Control in Sepsis
Localize and treat site of infection
Undrained pockets are lethal
Reviewed details of anticonvulsant therapy
– Agent known to contribute to renal stones!
– Repeat CT -> non-contrasted: left ureteric stone
– To OR for basket extraction
• Not possible -> stent placed
Questions about the case…
Appropriate supportive care (including antibiotics)?
Timely source control?
Candidate for activated Protein C?
Case: Activated Protein C
Infusion of activated Protein C started 24 hours
after admission to ICU
INR 2.4 -> 2.0 prior to aPC, 1.3 on infusion
Infusion x 96 hours total
– 12 hour window for OR (stent placed)
Stabilized clinically, inotropes weaned
Extubated day 7
Discharged for urologic followup
Lessons from Case 1
Case history
• 26-year-old female presents to ER
• Diagnosed with severe Gram-negative sepsis with multisystem
failure, septic shock, and ARDS
• Undergoes surgery to remove kidney stone
• Drotrecogin alfa (activated) infusion
Significance of case
• Condition initially unrecognized, resolved with treatment for
underlying condition
Case #2
73-year-old male, retired
Heavy smoker of 2 packs/day until five years ago
Presented with increased shortness of breath,
yellowish sputum production over the last week
and slight fever at 38.3°C two days prior to
admission
Chronic bronchitis on Ventolin®, Atrovent®
Last FEV1 in 1999 was 0.8 L/min
Pneumococcal pneumonia with severe sepsis, ICU
admission and mechanical ventilation in 1996 —
yearly vaccinations since
Present history:
Dark urine and hasn’t voided in last 8 hours
Has used Ventolin® inhaler 4 times in last couple of
hours
Physical examination:
23:00
On admission, 80 kg
Laboured breathing at 35/min, prolonged expiratory
time, accessory muscle use
Temperature 38.2°C
Distended internal jugulars, tachycardia at 110/min
NSR, BP 90/50
Physical examination (cont’d):
Positive HJ reflux
Fine crackles at both lung bases, swollen ankles
Right sided carotid bruit
Rest unremarkable
Investigations:
Outstanding lab results:
Na+ = 148
K+ = 3.2
BUN Urea = 15
PO2 = 130
Hg = 156
Hct = .47
Plat = 175 000
WBC = 12 500 no bands
ABG = 7.27/56/26/55
room air
Investigations (cont’d):
CXR: hyperfiltration, suspect bronchiectasis both
lung bases and doubtful left LL infiltrate
aPTT = 35/INR 1.3
Lactates normal
ECG right axis deviation, negative T waves V1-V4
anterior leads
Treatment, management and rationale:
23:40
BiPAP started in ER 12/5, 40% PIO2
Solumedrol 40 mg IV q 6 hours, cefuroxime 1 gm IV
q 8 hours and ICU consult
500 mL Pentaspan given over 1 hour after bladder
catheter revealed 20 cc of dark yellow urine with
absence of blood on strip reagent
Is this SIRS, sepsis, severe sepsis, or septic shock?
Is this patient a candidate for aPC?
Treatment, management and rationale (cont’d):
D5NaCl 0.9% + KCl 40 mg/L at 80 cc/hour
Not at risk for bleeding
Not a candidate for rhAPC
Lessons from Case 2
Recognize non-specific nature of SIRS criteria
Alternative causes for hypotension, oliguria
Need for appropriate search for presumed or proven
infection (COPD exacerbation doesn’t count)
Case 2: COPD
Jean-Gilles Guimond, MD
Case history
• 73-year-old male presents to ER with COPD/acute
tracheobronchitis, ?pneumonia
Case highlights
• Patient not a candidate for drotrecogin alfa (activated) therapy
because suffering from COPD exacerbation not sepsis
Significance of case
• Patient follows SIRS criteria but does not have sepsis
• Patient recovers; not treated with drotrecogin alfa (activated)
Case 3: Pneumococcal pneumonia
Bruce Light, MD
Case history
• 26-year-old woman, alcoholic, drug user
• Taken to emergency by friends; in confused state, bad cough with
yellow, bloody sputum, febrile
• Obvious right lower lobe pneumonia on chest x-ray
Case highlights
• Diagnosis: acute pneumococcal pneumonia with hypoxemic respiratory
failure, septic shock requiring vasopressor infusion, acute renal
insufficiency, and mild coagulopathy
• Treated with drotrecogin alfa (activated)
• Patient transferred to rehabilitation ward after 4 weeks
Significance of case
• “Typical” scenario
Case 4: Post-op infection
Claudio Martin, MD
Case history
• 67-year-old male undergoes coronary artery bypass surgery 3
weeks prior to presentation
• Re-admitted 3-weeks post-surgery for management of sternal
dehiscence associated with infection
• Develops respiratory distress; requires intubation and admitted
to ICU
• Started on drotrecogin alfa (activated)
• Requires chest tube for large pleural effusion (?infected)
• Drops Hb by 30 in 12 hours
• Recovers
Significance of case
• When to discontinue treatment transiently vs permanently
Case 5: AML, febrile neutropenia
Tom Stewart, MD
Case history
• Patient with AML, pancytopenic with severe neutropenia and
suspected lung infection
Case highlights
• Patient excluded from PROWESS study due to low platelet
count (15 000/mm3). Family approach physician about possible
treatment with drotrecogin alfa (activated)
• Case taken to clinical management team. Objections from
oncologist (effect on leukemia and risk of bleeding) and
pharmacist (cost and concern about use outside of guidelines)
• Drotrecogin alfa (activated) not given; patient dies
Significance of case
• Example of scenario where drotrecogin alfa not used