I- Introduction :
Septic shock is the result of & rsquo; acute circulatory failure, which alters the sustainable & rsquo; oxygenation and metabolism of different tissues and organs, in response to the body of the massive invasion by an infectious agent.
Despite the & rsquo; improving our knowledge of the pathophysiology of sepsis during the past two decades, these severe sepsis are aujourd & rsquo; hui still a major source of morbidity and mortality in intensive care units and mortality remains high and is close yet 50 %.
II- Definition and classification of septic states :
♦ The definition of sepsis is based on & rsquo; intensity of the response of & rsquo; s body & rsquo; infection.
It distinguishes sepsis "uncomplicated" of severe sepsis and septic shock, each corresponding to a clinical-biological entity precise way, Sepsis is defined as a systemic inflammatory response (or SIRS, Systemic Inflammatory Response Syndrome for) secondary to clinically or biologically documented infection.
At each stage of & rsquo; infection is a prognosis, specific epidemiological data and well-defined therapeutic measures to limit the growth and sustainability of the & rsquo; sepsis.
♦ diagnostic criteria SIRS, sepsis and septic shock
1- SIRS two or more of the following signs :
- Temperature > 38,3° C or < 36,0°C ;
- Cardiac frequency > 90/me ;
- Respiratory rate > 20/min ou PaC02 < 32 mmHg or mechanical ventilation ;
- leukocyte Count > 12000/mm3 or < 4000/mm3 or > 10 % immature cells.
2- Sepsis SIRS + infection "clinically or microbiologically documented"
3- severe sepsis sepsis + at least one sign of & rsquo; & rsquo hypoperfusion or, dysfunction d & rsquo; s body :
– circulatory function :
+ low blood pressure (NOT < 90 mmHg or PAM < 60 mmHg) ;
+ blood hyperlactataemia (lactate > 2 mmol/l ) ;
– respiratory function :
+ hypoxemia (Pa02 / FI02 < 300) ;
– higher functions:
+ presence of encephalopathy or delirium (score Glasgow < 14) ;
– renal function :
+ oligurie (urine output < 0,5 ml / kg / h despite persistent filling) ;
+ creatinine > 177 pmol/l (20 mg / l) ;
– Coagulation :
+ thrombocytopenia < 100 000/mm3 ;
– hepatic : hyperbilirubinémie > 34 pmol/l ;
4- Septic shock severe sepsis + persistence, despite appropriate vascular filling, from :
– low blood pressure (NOT < 90 mmHg, PAM < 60 mmHg),
– signs & rsquo; hypoperfusion (lactatémie > 4 mmol/l, oligurie, consciousness disorders,…).
III- pathophysiology :
Septic shock should be regarded as a biological succession & rsquo; events occurring extremely rapidly after & rsquo; abnormal introduction into the & rsquo; d & rsquo body; a foreign component d & rsquo; infectious origin; among microbial antigens, likely & rsquo; activate the immune system, include the & rsquo; endotoxin, lipopolysaccharide component of the outer membrane of Gram-negative bacteria, l & rsquo; lipoteichoic acid for Gram positive bacteria; Proteins mushrooms and certain viral protein components are also likely to & rsquo; activate the immune system.
The release of the toxin in the blood goes active phagocytic cells and driven mediator release pro-inflammatory and anti-inflammatory
❖ immunocompetent cells and mediators pro- and anti-inflammatory
NO:Nitric & rsquo; nitrogen; PAF: factor & rsquo; platelet activation; THE Ra: antagonist of the IL-1 receptor; sTNFr: récepteur TNF soluble; TGF-B: transformine growth factor-B; BPI: bacterial/permeability-inceasing protein; Sil-2r: soluble IL-2 receptor
This succession of & rsquo; events involves the immune defense system of the & rsquo; body, cellular mediators of this system and the consequences of & rsquo; action of these mediators on the various members, in particular, the heart and vascular system, lungs, liver, kidneys, the brain and the digestive system. So, the "shock" of severe sepsis represents a failure of the cardiocirculatory system secondary to decreased vasoconstrictor tone and myocardial contractility with hypovolemia.
❖ pathophysiological consequence
1- endothelial damage :
L & rsquo; endothelium is the guarantor of the quality of macrocirculation and microcirculation L & rsquo; endothelium provides four main functions :
- The regulation of vasomotor tone by synthesizing molecules vasorelaxant
- The maintenance of blood flow through the anticoagulant surface profibrinolytic
- The modulation of the & rsquo; inflammation of the & rsquo; apoptosis
- Finally, he participates in the & rsquo; angiogenesis.
During sepsis, the three essential properties of endothelial cells that are thrombomodulation, regulating vasomotion and modulation of the inflammatory reaction, are major revisions
l & rsquo; endothelium loses its anticoagulant properties and profibrinolytic to become procoagulant and antifibrinolytic frankly
L & rsquo; s achievement & rsquo; endothelium also results in a loss of character & rsquo; adaptation of vasomotor tone : septic vessel is vasoplegic. The ship n & rsquo; is able to & rsquo; adapt its tone to local stimuli, in particular to changes in infusion rate, endoluminal pressure or oxygen supply
Lesions of the & rsquo; endothelium eventually lead to the & rsquo; endothelial cell apoptosis. Thus his physical integrity and barrier function are met. It becomes hyperpermeable and promotes & rsquo; interstitial edema.
2- Coagulation :
- Side endothelial injury in sepsis lay bare the endothelium-under and allow direct contact between FT and circulating clotting factors. So, l & rsquo; exposure FT leads to the formation of & rsquo; a complex FT / factor VIIa whose resultant is the & rsquo; activation of the coagulation cascade
- Au total, l & rsquo; coagulation activation, Bankruptcy of natural anticoagulant systems and & rsquo; marked inhibition of fibrinolysis contribute to coagulation imbalance and anticoagulation during severe sepsis. They lead to an array of & rsquo; abnormal activation of coagulation and formation microthrombi making the bed d & rsquo; a lack of perfusion & rsquo; s body.
The final consequence of this activation is the occurrence of & rsquo; DIC is a secondary acquired syndrome, excessive systemic activation of coagulation.
3- FAILURE VASCULAR :
Vascular failure is central in the pathogenesis of septic shock. It can be divided into two major segments :
- endothelial dysfunction (endothelial injury, microcirculation disorders and hyperpermeability),
- vasoplegia and contractile abnormalities muscle vascular smooth.
Septic vessels becomes hyporesponsive, L & rsquo; vascular hyporesponsiveness may be defined by a lesser increase in blood pressure to the same dose of & rsquo; vasopressor
4- MYOCARDIAL FAILURE :
The pathophysiology of myocardial dysfunction is complex and involves proinflammatory cytokines, NO by indirect and probably irreversible action including through superoxide anions / peroxynitrite, would have a greater effect on the relaxation of myocardial contraction , impaired receptor |3- adrenergic, apoptotic phenomena and calcium abnormalities passing in particular by a decrease in the sensitivity of myocardial fibers.
this dysfunction, typically in the maximum 24 early hours, is reversible with return to normal of heart function usually in seven to ten days during the healing of the & rsquo; septic shock
5- ALTERATIONS AND METABOLIC DYSFUNCTION D & rsquo; ORGANS :
Organic alterations observed during septic shock related to the inflammatory process and the ensuing cardiovascular dysfunction. The severity of microvascular dysfunction seems to be the & rsquo; determining ultimate dysfunction d & rsquo; organs.
a- metabolic impairment :
Carbohydrate metabolism is most often changed. An initial phase of & rsquo; hyperglycaemia is associated with increased hepatic gluconeogenesis. It is followed by & rsquo; a marked hypoglycemia, associated with decreased liver function, d & rsquo increased secretion, insulin and an increase in & rsquo; peripheral glucose utilization
An increased protein breakdown may play a significant role in & rsquo; emergence of multi organ failure
b- lungs :
Two main mechanisms may explain the reduction in gas exchange
- direct action on the cell-capillary membrane with increased permeability and edema cell-interstiel
- a breach of regulatory mechanisms of hypoxic vasoconstriction Their clinical translation ARDS
c- splanchnic reached :
Intestinal pain seems to be very early in septic shock, the abnormality of the perfusion of the mucosa s & rsquo; accompanied & rsquo; an increase in intestinal permeability may be responsible for & rsquo; bacterial translocation
d- neurological :
may be the result of the & rsquo; liver failure, s & rsquo; kidney failure, shock and / or acute respiratory distress
IV- Diagnostic :
→ Clinical Diagnosis : clinically septic shock comprises two phases
- hot shock corresponding to an elevated heart rate in response to a decrease of vascular resistance induced by the release of vasodilator substances with hot ends, a bounding pulse and blood pressure observed hands increased differential discrete signs of dysfunction d & rsquo; organs are present( disorders & rsquo; mood, biological renal failure, abnormal liver function, hyperglycemia
- cold shock : corresponding to the & rsquo; enhancement of tissue damage including myocardial with vasoconstriction ,low blood pressure and pinch, a thready pulse and cyanosis of the extremities.
Severe acidosis related to the & rsquo; hypovolemia, decreased tissue perfusion, the failure of the & rsquo; use’02 and myocardial dysfunction
In fact the cold shock corresponds to uncorrected hypovolemia or underestimated or even heart failure
L & rsquo; assessment of severity is based on data of the & rsquo; clinical examination indicating & rsquo; & rsquo existence, organ failure and d & rsquo; a vital distress : NOT<90mmhg, not responding to the filling, tachycardia > 140 B/min , polypnoea > «30 cycle/min, and / or Sa O 2 < 90% despite the & rsquo; oxygen, disturbance of consciousness , cyanose, sweats and cliques dissemination signs of & rsquo; infection
→ Diagnostic paraclinique :
- Laboratory tests
L & rsquo; analysis of biological parameters can be found: blood lactate > 2meq/l, Fo2< 60mmhg, paint it < 130mmol/l, hematocrit < 30%, leucocytes <4000/mm3, creatinine > 20mg / l
The search for the & rsquo; infection is necessary for diagnosis. All referred to microbiological samples should be taken before starting the & rsquo; antibiotics, and without delay & rsquo; administration. Must perform 2 or more blood cultures
- morphological examination
Chest radiograph : can guide a worm infectious pneumonitis
L & rsquo; abdominal ultrasound : Search for signs of & rsquo; cholangitis, d & rsquo; obstacle in the urinary tract or peritonitis
L & rsquo; ASP can highlight the calculations (renal or biliary) or pancreatic calcifications
abdominal CT can guide worm acute pyelonephritis ,a renal abce or para-renal, or intra-abdominal
Brain CT and & rsquo; MRI looking & rsquo; affection neuromeningeal L & rsquo; echocardiography can highlight valvular vegetation
- hemodynamic exploration
- Installation d & rsquo; a radial catheter : continuously tracks the change in PA
- A central venous catheter that enables followed by PVC and the & rsquo; administration of vasoactive therapy
- L & rsquo; echocardiography: transthoracic or transesophageal confirms the volume disorders, the presence of & rsquo; ventricular dysfunction and directs the etiological diagnosis
- The SWAN-Ganz catheter measures the pressure in the right cavities and & rsquo; pulmonary artery
V- Treatment :
Treatment d & rsquo; a patient with septic shock takes place under surveillance : d & rsquo; an ECG, able & rsquo; Pulse oximetry, Monitoring blood pressure, a central venous catheter which allows the monitoring of the PVC and the & rsquo; administration of vasoactive therapy, a catheter SWAN-GANZ when the hemodynamic situation remains unstable, regular measurement of blood gases, measuring the & rsquo; acid-base balance and lactate ratio / pyrivate allows & rsquo; evaluate & rsquo; tissue oxygenation
– antibiotic treatment : Empirical must be directed against the largest number of germs that justifies the use of & rsquo; a double or a triple combination for d & rsquo; bring many benefits: broadening the spectrum of & rsquo; activity, obtaining & rsquo; antibacterial synergy with increased bactericidal rate, preventing or limiting risk selection or & rsquo; emergence of mutant or resistant strains
– L & rsquo; oxygen : is essential, administration up until & rsquo; to use d & rsquo; mechanical ventilation
– A daily intake of 200 g de glucose, often associated with the & rsquo; insulin, can cover the immediate energy needs
– Correction of the & rsquo; baking administration acidosis for PH <7,20
– Corticosteroid therapy in patients with severe septic shock requiring high doses of & rsquo; vasoactive agent : hémisuccinate d’hydrocortisone 200 at 300 mg / j, the duration of treatment is 5 days in case of clinical response , Beyond 72 hours l & rsquo; no hemodynamic response justifies & rsquo; stopping treatment
– hemodynamic therapy
Resuscitation should be started immediately in any patient with low blood pressure or elevated lactate to the top 4 mmol/l, and even before the & rsquo; patient admission to intensive care industry.
The objectives are :
- a central venous pressure (PVC) between 8 and 12 mmHg ;
- mean arterial pressure (PAM) greater than or equal to 65 mmHg ;
- diuresis to 0,5 ml / kg / hour ;
- saturation 02 venous blood (SV02 in the measured & rsquo; right atrium) better than 70 % or greater 65 % in mixed venous.
→ The vascular filling
- Is the & rsquo; initial stage , its main objective is to & rsquo; optimize the preload of the left ventricle to d & rsquo; increase the transport & rsquo; oxygen by increasing cardiac output
The fluid loading may be performed by two types of solutes :
crystalloid (isotonic or hypertonic) and colloids (natural or synthetic)
Blood transfusion is performed for threshold & rsquo; hemoglobin between 8 and 10 g/dl
The filling should be continued until & rsquo; & rsquo to; obtaining & rsquo; PVC > 8 mmHg and d & rsquo; a WFP > 65 mmHg.
→ LES CATECHOLAMINES
- Their goal is to restore perfusion pressure, d & rsquo; ensure cardiac output to transport d & rsquo; sufficient oxygen
- Because d & rsquo; a large interindividual variability, l & rsquo; gradual increase in dosage is recommended to d & rsquo; get a PAS 90 PAM mmHg or two 60 to 65mmhg
- dopamine : dose 5 10&/kg/mn: B effect resulting in an increased volume of & rsquo; stroke and cardiac output, dose ranging from at 10 at 50 &/kg / min vasopressor effects
- norepinephrine : powerful vasopressor agent used in cases of refractory shock dopamine
- L & rsquo; adrenaline : and has effects 3 adrenergic increases the vasoconstrictor tone and cardiac output
- La dobutamine : properties 3 1 powerful agonists has been recommended to treat myocardial depression
at dopexamine :a main adrenergic type action (3 2 has been proposed for the treatment of & rsquo; congestive heart failure
→ SPECIFIC TREATMENT TO CONTROL THE INFLAMMATORY RESPONSE
SYSTEM PROTEIN C
Known as physiological inhibitor of thrombin, the system of protein C has anticoagulant properties, fibrinolytic, anti-inflammatory and anti- apoptotiques.
Cours du Dr Lamara – Faculty of Constantine