Professional Documents
Culture Documents
Case:
A 71 year old woman who is dialysis dependent presents with fevers, malaise, and hypotension (SBP < 70 mm Hg). Blood cultures grow out S. aureus. Within hours of admission, she goes into florid pulmonary edema and enzymes are positive for an acute myocardial infarction. The next day her liver enzymes skyrocket and she goes into DIC. The patient dies within 48 hours of presentation despite aggressive intervention.
Epidemiology of Sepsis
Major cause of morbidity and mortality Leading cause of death in non-coronary ICUs 13th leading cause of death in the US overall More than 700,000 cases of severe sepsis in US annually Annual cost in US estimated at $17 billion
Sepsis: Mortality
Study
Brun-Buisson, 1995 Abraham, 1997
Condition
Severe sepsis Severe sepsis Septic shock Severe sepsis/ Septic shock Septic shock
Natanson, 1998
Friedman, 1998
49.7% (10,694)
More than 1400 people lose their lives to severe sepsis every day.
Septic shock Poisons & toxins (i.e. overdose) Anaphylaxis Neurogenic shock Endocrinologic shock
Sepsis
Clinical Evidence of Infection
PLUS
Hyperthermia/Hypothermia (> 38.4 or < 35.6) Tachycardia (> 90 beats / minute) Tachypnea (> 20 breaths / minute) WBC count abnormalities
Sepsis Syndrome
Sepsis
PLUS Evidence of Altered Organ Perfusion:
z z z z
Acute mental status changes Hypoxemia (pO2 / FIO2 < 280) Oliguria (< 0.5 ml / kg / hour) Serum lactate (above normal limits)
z z z z
Disseminated Intravascular Coagulation (DIC) Adult Respiratory Distress Syndrome (ARDS) Acute Renal Failure Acute Hepatic Failure Acute CNS Dysfunction
Sepsis
Sepsis Syndrome
MODS
Death
13% mortality for the sepsis syndrome 28% mortality for patients presenting with shock 43% mortality for patients who developed shock after presenting with the sepsis syndrome
Kallikrein-Kinin Stimulation
PMN Activation
Shock
MODS
Death
Anti-endotoxin Therapy
Several thousand patients have now been included in clinical trials of new agents for sepsis... none of the interventions has has shown efficacy in prospectively defined study groups...
Abraham & Raffin [JAMA 1994 ]
What About Steroids? It is now widely accepted that glucocorticoids should not be used in the treatment of septic shock.
Bone [Clin Micro Rev, 1993]
In patients with relative adrenal insufficiency, the group that received the steroids did better as measured by 28 day survival
z
73 deaths (63%) in the placebo arm compared to 60 deaths (53%) in the treatment arm [JAMA 2002; 288(7):862-871]
5-20 micrograms/minute 5-20 micrograms/minute 2-20 micrograms/kg/minute 5-15 micrograms/kg/minute 2-20 micrograms/minute
Supportive Measures
Transfusions
PRBCs when hemoglobin < 7 z Platelets occasionally needed
z
Albumin
z
Percutaneous drainage Incision and drainage Incision and debridement Pull lines (complete catheter exchange) Consider removing artificial joints, valves, and/or grafts Remove or bypass obstruction (e.g. stones)
Necrotic tissue
z
Foreign bodies
z z z
PLUS
Antipseudomonal aminoglycoside, OR Antipseudomonal fluoroquinolone
Antipseudomonal Beta-lactams
Cefepime (Maxipime)
z
Ticarcillin (Ticar)
z
Piperacillin (Pipracil)
z
Antipseudomonal Beta-lactams
Ticarcillin-clavulanate (Timentin)
z
Piperacillin-tazobactam (Zosyn)
z
Imipenem-cilastatin (Primaxin)
z
Meropenem (Merrem)
z
Pharmacodynamics
For beta-lactam antibiotics, efficacy depends on the time that the concentration of the drug is over the minimum inhibitory concentration (MIC)
z z
Critical parameter is time above MIC Giving higher amounts of the drug wont help, its the frequency that is important
Critical parameter is AUC/MIC High concentrations will improve efficacy Post-antibiotic effect is seen
Georges Favorite
Cefepime 2 g IV q 8 hours and Tobramycin 5 mg/kg IV q 24 hours
(but substitute ciprofloxacin 400 mg IV q 12 hours for tobramycin if renal insufficiency is present)
Conclusions (1)
Sepsis causes major morbidity & mortality Shock does not equal sepsis Host factors are important predictors of which patients will progress to septic shock SIRS (the systemic inflammatory response syndrome) is caused by a complex cascade that begins with exposure to bacterial cell membrane products such as Lipid A
Conclusions (2)
Pathogenesis of septic shock has suggested numerous targets for very promising, but so far unrewarding, therapeutic modalities Hemodynamic support, O2 and mechanical ventilation, prompt removal of the source of infection, and empiric broad spectrum antibiotics continue to be the best therapy for sepsis, the sepsis syndrome, & septic shock
Thank you!