Blood Poisoning (Sepsis): Drug Therapy

Therapeutic target

  • Avoidance of complications

Therapy recommendations

  • The therapy of sepsis is complex. In this context, “Drug therapy” is one of the mainstays. In addition, causal therapy (see under “Further Therapy” and “Supportive Therapy” (also see under “Further Therapy”) is of great importance.
  • In the presence of septic shock: for hemodynamic stabilization in patients with sepsis-induced hypoperfusion (decrease in blood flow (perfusion) within a vessel or vascular segment), administer an intravenous crystalloid solution within the first 3 hours (at least 30 ml/kg in the first 3 hours; continue only if signs of hypoperfusion are present) and, if necessary, administration of vasoactive substances (see below “Further Therapy” and “Supportive Therapy”).
  • If necessary, surgical therapy of the underlying disease (focal rehabilitation).
  • Adequate intravenous antibiotic therapy (broad-spectrum therapy with one antibiotic or several antibiotics): this should be started as early as possible – at best in the first hour after diagnosis. Before this, however, blood cultures (BK; at least 3-BK pairs at intervals of at least 60 min) should be taken. Note: In up to 30% of the diseases can not be a confirmed pathogen detection in sepsis.
  • Therapy must be based on local microbiological resistance patterns and evaluated regularly.
  • The current S-3 guideline recommends that if the patient improves clinically within the first 72 hours, even without pathogen detection, initial combination therapy is de-escalated to monotherapy.
  • Duration of therapy longer than 7-10 days is usually not required.
  • There are differentiated agent recommendations, which are not further detailed here, at:
    • Unknown source of infection
    • Pneumogenic (“originating from pneumoniae/pneumonia“) sepsis.
    • Intra-abdominal (“originating from the abdominal organs”) sepsis.
    • Urogenital (“originating from the urinary tract or reproductive organs”) sepsis.
    • Sepsis originating from the skin / soft tissues.
    • Sepsis due to Staphylococcus aureus [longer treatment duration (at least 14 days) required!]
    • Sepsis due to Staphylococcus epidermidis
    • Active substances for special pathogens
  • Supportive therapy (supportive therapy): hemodynamic (“flow mechanics of the blood concerned”) stabilization (volume therapy) of the patient and achievement of an adequate cellular oxygen supply (see below) https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-24-27-june-2019
  • In the context of intensive care monitoring regular determination of: central venous oxygen saturation, MAP (English : mean arterial pressure, short: MAP; mean arterial pressure, short MAD), diuresis, ZVD (central venous pressure) and lactate.
  • See also under “Further therapy”

Further notes

  • The first methicillin-resistant Staphylococcus aureus (MRSA) strain resistant to the reserve antibiotic vancomycin has emerged in Brazil
  • Patients with intra-abdominal infections (e.g., due to complicated appendicitis or after intestinal perforation due to inflammatory bowel disease) usually require only short-term antibiotic therapy (4 days!) after successful surgical focal decontamination. Early cessation of antibiotic therapy did not pose a life-threatening risk to patients, even if body temperature, leukocyte count, and bowel function had not yet normalized.
  • In urogenital sepsis, antibiotic resistance rates were lowest for carbapenems (8%)
  • A meta-analysis of patients with severe sepsis or severe septic shock showed that hospital mortality was significantly lower (RR 0.74 [0.56-1.00], p =0.045) and clinical cure was significantly higher (RR 1.20 [1.03-1.40], p =0.021) in the group with continuous administration of beta-lactam antibiotics.
  • Early-goal-directed therapy (EGDT) achieved a reduction in in-hospital mortality compared with standard treatment. The therapy involves a strict protocol for administration of fluid, vasopressors or inotropics, and blood products to achieve defined targets:
    • Arterial blood pressure (MAD ≥ 65 mmHg).
    • central venous pressure (8-12 mmHg)
    • Central venous saturation (> 65%)
    • Adequate diuresis (> 0.5 ml/kg/h)

    Within the first six hours of septic shock [see “Supportive Therapy” below].

  • In a randomized controlled trial, ventilated patients with septic shock received either hydrocortisone (200 mg/day i. .v via perfusor) or placebo for a maximum of 7 days or until death or ICU discharge. Results: hydrocortisone did not reduce 90-day mortality (death rate) in septic shock.
  • High-dose vitamin C therapy (intravenous vitamin C at the dose of 50 mg/kg every 6 hours for 96 hours): all three primary efficacy endpoints and 43 of 46 secondary endpoints were missed in a randomized controlled trial; however, ICU recovery was accelerated (seven rather than 10 days) and patient survival was significantly improved Deaths: 29.8% versus 46.3%).

Supportive therapy

Hemodynamic stabilization

The following target values should be achieved:

  • Central venous oxygen saturation (ScvO2) of: > 70%; oxygen saturation (SpO2) > 94%.
  • MAP (English : mean arterial pressure, for short): ≥ 65 mmHg.
  • Diuresis (urine output): ≥ 0.5 ml/kh KG/h
  • CVP (central venous pressure): 8-12 mmHg under mechanical ventilation.
  • Lactate: ≤ 1.5 mmol/l or drop.

To do this, proceed as follows:

  • Volume therapy: initially, volume substitution is recommended; the dose depends on the effect and tolerance.
    • Administration of 30 ml/kg electrolyte solutions (crystalloid fluid) in the presence of hypotension (“low blood pressure”) or lactate ≥ 4 mmol/l
  • Vasopressor (substances used to raise or support blood pressure) of first choice: norepinephrine
    • When adequate blood pressure cannot be achieved with norepinephrine alone → addition of either vasopressin or epinephrine to norepinephrine.
  • Treatment of refractory hypotension in adults with sepsis or other distributive shock: Angiotensin II (synthetic variant of angiotensin II, the most potent endogenous vasopressor).
  • In tachycardic arrhythmias (cardiac arrhythmia in which the heart rate is too fast): β1-selective beta blockers.

Renal replacement procedures (see under “Other Therapy”).

Airway management/ventilation (see under “Further therapy”).

Thromboprophylaxis

  • Prophylaxis of venous thromboembolism (VTE) using unfractionated heparin (UFH) or low-molecular-weight heparin (NMH) is recommended.Note: A thromboembolism is said to occur when a blood clot (thrombus) detaches from the wall of a blood vessel and is transported further within the bloodstream. Subsequently, this gets stuck in a blood vessel and blocks it. As a result, the area behind the blockage is no longer supplied with blood. When this occurs in one or more pulmonary artery branches (branches of the pulmonary artery), it is called a pulmonary embolism.

Bicarbonate

  • Bicarbonate therapy cannot be recommended in hypoperfusion-induced lactic acidosis (form of metabolic acidosis in which a drop in blood pH is due to accumulation of acid lactate) with a pH > 7.15

Blood products

  • Red blood cell concentrates (blood products derived from whole blood and composed predominantly of red blood cells) should be administered when Hb (hemoglobin; blood pigment) is 7.0 g/dL or higher, in the absence of relevant cardiac disease, and tissue perfusion is normal
    • Hb should be raised to values between 7.0-9.0 g/dl
  • Erythropoietin (endogenous hormone that stimulates the formation of red blood cells (erythrocytes) in the stem cells of the bone marrow) cannot be recommended
  • Prophylactic platelet transfusion in the absence of other bleeding risks only when platelet counts <10,000/μl.
  • Fresh frozen plasma (FFP for short; a blood product obtained from human donor blood that contains the liquid and dissolved components of the blood; the cells of the blood (erythrocytes/red blood cells, leukocytes/white blood cells, platelets/thrombocytes) have been largely removed by centrifugation) should not be used without a clinically manifest bleeding tendency

Sedation, analgesia/pain relief, delirium.

  • Levels of sedation (calming) and analgesia (pain relief; analgesia) should be reviewed regularly; validated scoring systems should be used
  • Etomidate should not be used as an induction hypnotic (induction sleep agent)
  • Muscle relaxants should not be used

Adjunctive therapy

Glucocorticoids

Therapy with hydrocortisone (200-300 mg/d) may now be considered as an ultima ratio only in refractory courses. However, the quality of evidence is considered low. Insulin therapy

Intravenous insulin therapy can be considered for values > 150 mg/dl (> 8.3 mmol/l). Recombinant activated protein C (rhAPC).

The rhAPC may be recommended in patients with an APACHE II score > 25 points.Therapy with heparin should not be interrupted with rhAPC. Immunoglobulins

IgM-enriched immunoglobulins may be considered in severe sepsis/septic shock in adults. Selenium

Selenium may be considered in patients with severe sepsis/septic shock. Therapeutic approaches that cannot be recommended:

  • Antithrombin
  • Ibuprofen
  • Growth hormones
  • Prostaglandins
  • Pentoxifylline
  • N-acetylcysteine
  • Granulocyte colony stimulating factor
  • Protein C concentrates
  • Use of hydroxyethyl starch for intravascular volume replacement therapy.