Sepsis

Is systemic inflammatory response (SIR) to infection (Rackow EC., 1986). It represents progressive stages of the same illness in which a systemic response to an infection mediated by endogenous mediators may lead to a generalized inflammatory reaction in organs remote from the initial insult and eventually to end organ dysfunction and /or failure (Bone RB, et al., 1998). Sepsis remains an important and life-threatening problem as it is the most common cause of death in the intensive care unit (Parrillo JE, et al., 1990). Also it is possible that many deaths due to sepsis are attributed to underlying diseases when mortality statistics are complied (Young, L.s., 1990).

The use of the term sepsis is not restricted to a systemic inflammatory syndrome secondary to bacterial infection, but to this syndrome resulting from any microorganisms and/ or its products (toxins). The term sepsis is applicable only when the systemic response is clinically relevant, which can manifest in a variety of situations of increasing complexity such as : (a) severe sepsis, understood as sepsis associated with organ failure, hypoperfusion (which includes, but is not limited to lactic acidosis, oliguria or an acutely altered state of consciousness) and hypotension; (b) septic shock, understood as sepsis associated with hypoperfusion alterations, but with persistent hypotension even after suitable volumetric resuscitation, and (c) multiple organ failure syndrome (MOFS), which may represent the final stage of the sever systemic inflammatory response. However, the limits which separate sepsis from severe sepsis and this from septic shock are not easily detected in clinical at ICUs, or

even from a conceptual point of view. (Levy MM, et al, 2003; Despond O, et al, 2001).

Diagnosis of sepsis

Diagnosis of sepsis is based on a high level of suspicion, which demands a minutely detailed collection of information on present status and medical history of the patient, a good clinical evaluation, certain laboratory tests, in addition to rigorous clinical monitoring of the patient. There are three key difficulties associated with the diagnosis of infection in patients who have sepsis: і) establishing infection as the primary cause which is the first important step in the diagnosis, this will exclude non-infective causes of SIRS ((M.LIewelyn, et al., 2001). іі) localizing the site of infection: The identification of the primary site of infection is a critical part of the work-up of the septic patient. Together with the gram stain of specimens obtained from any site suspected of infection, it is probably the single most important information in guiding the choice of antibiotic therapy (Sands KE, et al., 1997; Boillot A, et al., 1995; Bernard GR, et al., 1997). ііі) interpreting the microbiological findings (M.LIewelyn, et al., 2001).

The International Sepsis Definitions Conference amplified the list of possible clinical and laboratory signs of sepsis which may allow for more efficacious suspicion and management. (Paulo R, et al., 2003). The symptoms and signs that should lead to suspect sepsis are as follow:

General variables:
- Fever (core temperature > 38.3 °C)

- Hypothermia (core temperature < 36 °C) - Heart rate > 90 min-1 or > 2 SD above the normal value for age
- Tachypnea
- Altered mental status
- Significant edema or positive fluid balance (> 20 ml/kg over 24 hrs)
- Hyperglycemia (plasma glucose > 120 mg/dl or 7.7 mmol/l) in the absence of diabetes

Inflammatory variables:
- Leukocytosis ( WBC count >12,000/mm3)
- Leukopenia (WBC count < 4,000/ mm3) - Normal WBC count with > 10 % immature forms
- Plasma C- reactive protein > 2 SD above the normal value
- Plasma procalcitonin > 2 SD above the normal value

Hemodynamic variables:
- Arterial hypotension (SBP < 90 mm Hg, MAP < 70, or an SBP decrease > 40 mm Hg in adults or <2 SD below normal for age) - Mixed venous oxygen saturation SvO2 > 70 %
- Cardiac index > 3.5 1/min-1/M -23

Organ dysfunction variables:
- Arterial hypoxemia (PaO2/FIO2< 300) - Acute oliguria (urine output < 0.5 ml/kg -1/hr -1 or 45 mmol/1 for at least 2 hrs) - Creatinine increase > 0.5 mg/dl
- Coagulation abnormalities ( INR >1.5 or aPTT > 60 secs)
- Ileus (absent bowel sounds)

- Thrombocytopenia (platelet count < 100,000/mm3) - Hyperbilirubinemia (plasma total bilirubin > 4 mg/dl or 70 mmol/l)

Tissue perfusion variables:
- hyperlactatemia (>1 mmol/l)
- Decreased capillary refill or mottling
(Levy MM, et al., 2003)

Causative organisms:

Sepsis and septic shock, caused by gram-negative, gram positive bacteria, fungi, viruses, and parasites, have become increasingly important over the past decades (Glauser, et al., 1991). In the United States, the septicemia rates more than doubled between 1979 and 1987 causing up to 250,000 deaths annually (Opal, et al., 1999 ; Parillo, et al., 1993). The proportion of infections due to gram-negative bacteria varied between 30 and 80% and that of infections due to gram-positive bacteria varied between 6 and 24% of the total number of cases of sepsis, with the remainder being accounted for by other pathogenic organisms (Glauser, et al., 1991).

Gram-negative sepsis

Was a relatively rare clinical diagnosis only a few decades ago, but today it is the most important infectious disease problem in hospitals. Nearly 80 % of all documented epidemics were caused by gram-negative bacilli. ( Roger C and Bone ., 1993). Estimated mortality from sepsis of gram-negative etiology ranges from 20 to 50 % of the overall total number of septic death. (Wenzel, R. P., 1988; Young, L. S., 1990).

Most gram negative infections were caused by Enterobacteriaceae with Escherichia coli which is the most commonly isolated pathogen, followed by klebseilla and enterobacter species. Although pseudomonas species were encountered somewhat less frequently, pseudomonas aeruginosa has consistently been associated with the highest mortality rate among all causes of bacteremic infection. (Young, L. S., 1990)