Difficulty in patient enrollment

The investigators will examine the toxicity of therapeutic doses of paracetamol in patients in severe sepsis. Patients with fever and severe sepsis will be randomized to receive paracetamol or dypirone. The investigators will monitor blood glutathione and liver enzymes to look for potential toxicity.

Paracetamol is metabolized in liver using the glutathione system. This detoxification system is depressed during severe illness such as sepsis, trauma etc. The study will examine the toxicity of therapeutic doses of paracetamol in patients in severe sepsis. We believe that during sepsis, paracetamol metabolites are not fully detoxified and therefore are toxic to the patient.

Patients with fever and severe sepsis will be randomized to receive paracetamol or dypirone. The investigators will monitor blood glutathione (as a surrogate marker for liver glutathione), liver enzymes and various clinical data (such as length of hospitalization) to look for a potential toxicity.

Inclusion Criteria:

• age>18y

• hospitalized to int. med. dept. or ICU

• body temp>38 and one or more from the following:

  1. pulse>90 bpm
  2. resp. rate>20/min or PaCO2<32 mmHg
  3. WBC>12000 or <4000

• one of the following:

  1. hypotension
  2. disturbed end-organ perfusion (confusion, oliguria, lactic acidosis etc.)

Exclusion Criteria:

• acute / chronic liver disease
• acute CNS disorder
• current isoniazid treatment
• alcoholism
• active malignancy
• pregnancy
• TPN or PPN