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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
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 LFTs 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
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?
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
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 38.3C 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 hasnt 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 38.2C Distended internal jugulars, tachycardia at 110/min NSR, BP 90/50
Positive HJ reflux Fine crackles at both lung bases, swollen ankles Right sided carotid bruit Rest unremarkable
Investigations:
Hct = .47 Plat = 175 000 WBC = 12 500 no bands ABG = 7.27/56/26/55 room air
Investigations (contd):
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
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?
D5NaCl 0.9% + KCl 40 mg/L at 80 cc/hour Not at risk for bleeding Not a candidate for rhAPC
Recognize non-specific nature of SIRS criteria Alternative causes for hypotension, oliguria Need for appropriate search for presumed or proven infection (COPD exacerbation doesnt count)
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 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