Therapy

The general goals of therapy are:

1. Stabilization of hemodynamics

2. Improvement of oxygen saturation and utilization

3. Sufficient organ perfusion

4. Improved organ function (heart, lung, liver, kidney)

5. Antimicrobial treatment of sepsis

6. Sanitization of the focal source of infection

7. Essential steps of therapy (Evans 2001; Hotchkiss and Karl 2003; Rivers et al. 2001; Reinhart et al. 2004; Russel 2006) are compiled in Table 5.4

Table 5.4. Recommended therapeutic approach to patients suffering from urosepsis

Patients should immediately be transferred to the ICU

1. Volume replacement: infusion of 1-2 l of electrolyte solution over 1-2 h; goal: central venous pressure (CVP) 8-12 mmHg, mean arterial blood pressure >65 mmHg, but <90 mmHg Blood transfusion in case of central venous oxygenation < 70 % and of hematocrit < 30; optimal: fresh erythrocyte concentrates; goal: hemoglobin value > 7-< 10 g/100 ml whole blood, hematocrit >30

In case of hypalbuminemia (< 2 g/100 ml), the additional infusion of albumin solutions has been suggested but is still controversial

2. Controlled and assisted ventilation: tidal volume, 6 ml/kgbody weight; goal: arterial oxygen saturation 93 %, central venous oxygen saturation >70%. If <70%, administration of dobut-amine (initially 2.5 |g/kg/min, after 30 min each, increase by 2.5 |g/kg/min; maximum, 20 |g/kg/min)

3. Administration of vasopressors: if mean arterial pressure (MAP) <65 mmHg, give dopamine, 1-3 |g/kg/min, or noradrenaline (norepinephrine), 0.1 -1.0 |g/kg/min, as a continuous i.v. infusion

4. Control of urine excretion; goal: >30 ml/h; if necessary, give furosemide in order to inhibit tubular re-resorption (therapeutic value not evidence-based). Tight control of blood glucose; goal: 80-110 mg/100 ml; exact stabilization with intensive insulin therapy (anti-apoptotic effect) (Evans 2001; Russell 2006; Van den Berghe et al. 2001)

5. Antimicrobial therapy: if possible, targeted (pathogen identified, sensitivity determined), otherwise calculated, or initially untargeted (wide-spectrum): reserve beta-lactam antibiotics i.v., e.g., cefotaxime, 3x2-4 g/day, or ceftazidime, 3x1-2 g/ day, or ceftriaxone, 2 x 2 g at day 1, then 1x2 g/day, plus aminoglycoside i.v., e.g., gentamicin, 1 x 240- 320 mg/day, by infusion. Monitor blood levels of aminoglycoside, trough concentration should be < 1 - 2 |g/ml, and creatinine levels, three to seven times/week (Bodmann and Vogel 2001; Gilbert et al. 2006)

6. After stabilization of cardiovascular function and start of antimicrobial therapy, removal of the infectious focus is mandatory. Abscesses have to be drained, and pyonephrosis has to be treated either by intraureteral JJ catheters or percutaneous nephrostomy. A Foley catheter should be inserted in any case

7. Supportive measures: for patients in septic shock and/or those with proved adrenocortical insufficiency (serum cortisol level < 15 |g/100 ml; corticotropin test: within 30-60 min after i.m. or i.v. injection of 250 |g of adrenocorticotropin hormone, increase of serum cortisol level <9 |g/100 ml), the i.v./i.m. administration of hydrocortisone (4x50 mg/day), or equivalent, is indicated (Cooper and Stewart 2003; Hamrahian et al. 2004; Rhen and Cidlowski 2005; Russell 2006)

8. In order to inhibit imminent disseminated intravascular coagulation (reduced levels of plasma protein C) in cases of severe sepsis, recombinant human activated protein C (drotrecogin alpha-activated) with a dose of 24 |g/kg/h as a continuous i.v. infusion for 96 h is recommended (Bernard et al. 2001; Dellinger 2003; Matthay 2001; Opal et al. 2003). The drug is approved for patients with an Apache II score of >25, but should not be used in patients with severe sepsis who are at low risk for death, such as those with single-organ failure or an Apache II score <25 (Abraham et al. 2005; Parrillo 2005; Russell 2006). The substance has antithrombotic, anti-apoptotic, antiinflam-matory, and pro-fibrinolytic properties. Potential adverse effect is hemorrhagic diathesis

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