Septic shock Babak Tamizi Far M.D Isfahan university of medical sciences
Definitions Used to Describe the Condition of Septic Patients
Approximately 750,000 cases of severe sepsis or septic shock occur every year in the United States. Sepsis causes as many deaths as acute myocardial infarction, and septic shock and its complications are the most common causes of death in noncoronary intensive care units.
Septic shock may be caused by grampositive or gram-negative bacteria, fungi, and, very rarely, protozoa or rickettsiae. Increasingly common causes of septic shock are gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus, vancomycinresistant enterococci, penicillin-resistant Streptococcus pneumoniae, and resistant gram-negative bacilli.
Pathobiology Initially, septic shock activates inflammation, thereby leading to enhanced coagulation, activated platelets, increased neutrophils and mononuclear cells, and diminished fibrinolysis
Procoagulant response in sepsis
Clinical Manifestations Cardiovascular dysfunction decreased preload (because of decreased intake, fluid losses, third spacing resulting from increased permeability, and venodilation), decreased afterload, and often decreased ventricular contractility.
Diagnosis Even as the diagnostic evaluation is beginning, the initial assessment of a critically ill patient must focus immediately on the airway (need for intubation), breathing (respiratory rate, respiratory distress, pulse oximetry), circulation (heart rate, blood pressure, jugular venous pressure, skin perfusion), and rapid initiation of resuscitation
Vital signs and the leukocyte count Arterial blood gases and lactate levels are useful immediate complementary tests
Algorithm for clinical and laboratory evaluation and management approach to septic shock
The major differential diagnoses of classic septic shock are other nonseptic causes of SIRS, such as acute pancreatitis,acute respiratory distress syndrome, aspiration pneumonitis, multiple trauma, and recent major surgery without infection
The differential diagnosis of septic shock must include the other causes of shock: hypovolemic, cardiogenic, and obstructive shock
shock (from internal or external fluid losses, hemorrhage) present with a suggestive history and signs of hypovolemia (low jugular venous pressure) and skin hypoperfusion (cool, clammy, cyanotic extremities).
Cardiogenic shock (resulting from myocardial infarction or acute on chronic congestive heart failure or occurring after cardiovascular surgery) is suggested by the history, signs of increased filling pressure (increased jugular venous pressure, crackles, S3, pulmonary edema, cardiomegaly) and skin hypoperfusion
Obstructive shock (from pulmonary thromboembolism, cardiac tamponade, pneumothorax) manifests similarly to cardiogenic shock.
Initial Antimicrobial Therapy for Severe Sepsis with No Obvious Source in Adults with Normal Renal Function
FIGURE 109-4 Ongoing critical care support and management in septic shock
Respiratory Therapy require oxygen initially, and many will require mechanical ventilation. Mechanical ventilation is required in most patients who have septic shock because acute lung injury is the most common complication. Lung protective ventilation (mechanical ventilation that minimizes lung injury by using relatively low tidal volume, i.e., <6 ml/kg of predicted body weight) decreases mortality of acute lung injury and acute respiratory distress syndrome
Patients who require ventilation need adequate but not excessive sedation, which can worsen hemodynamic instability, prolong ventilation, and increase the risks of nosocomial pneumonia. Sedation should be titrated using objective assessment. Daily interruption of sedation decreases the duration of mechanical ventilation and intensive care. Neuromuscular blocking agents should be avoided because of the risks of prolonged neuromuscular dysfunction.
Circulatory Therapy Ventilator therapy is indicated for progressive hypoxemia, hypercapnia, neurologic deterioration, or respiratory muscle failure. Sustained tachypnea (respiratory rate, >30 breaths/min) is frequently a harbinger of impending respiratory collapse; mechanical ventilation is often initiated to ensure adequate oxygenation, to divert blood from the muscles of respiration, to prevent aspiration of oropharyngeal contents, and to reduce the cardiac afterload.
The results of recent studies favor the use of low tidal volumes (6 ml/kg of ideal body weight, or as low as 4 ml/kg if the plateau pressure exceeds 30 cmh2o). Patients undergoing mechanical ventilation require careful sedation, with daily interruptions; elevation of the head of the bed helps to prevent nosocomial pneumonia. Stress-ulcer prophylaxis with a histamine H2receptor antagonist may decrease the risk of gastrointestinal hemorrhage in ventilated patients.
Fluids should be used to maintain a central venous pressure 8 to 12 mm Hg; at present, no convincing data indicate that albumin is better than normal saline solution.
Vasopressors (e.g., norepinephrine, 1 to 50 μg/minute; epinephrine, 1 to 30 μg/minute) should be added if the mean arterial pressure is less than 65 mm Hg. Dobutamine (2.5 to 20 μg/kg/minute) is required if central venous pressure, mean arterial pressure, and hematocrit are optimized yet the central venous oxygen saturation remains less than 70%.
If hypotension persists despite adequate fluid resuscitation, then vasopressors such as norepinephrine (1 to 50 μg/minute) are added.
The overall goal is to achieve an adequate mean arterial pressure (>65 mm Hg), central venous pressure, and mixed venous oxygen saturation while other indices of adequate perfusion are monitored such as hourly urine output (>0.5 ml/kg/hour), arterial lactate levels (<2 mmol/l), mental status, and skin perfusion.
A reasonable approach is to use a hematocrit level of 30% as a threshold to erythrocyte transfusion for the first 6 hours and then to lower the threshold to a hemoglobin of 7 to 9 g/dl for the rest of the hospital course, except in patients with underlying cardiac disease.
After appropriate cultures are obtained, intravenous broad-spectrum antibiotics should be administered on an emergency basis
Antibiotics If a causative organism is identified (>20% of septic patients have negative cultures), then the antibiotic regimen should be narrowed to decrease the emergence of resistant organisms.
The duration of antibiotics should be guided by the cause of septic shock, but patients generally require 10 to 14 days of therapy.
Corticosteroids hydrocortisone may decrease the duration of required vasopressor support in septic shock these drugs may increase survival in septic patients who have an increase in their serum cortisol levels to 9 μg/dl or less after a 250-μg corticotropin stimulation
The recommended treatment is hydrocortisone (50 mg intravenously every 6 hours) plus fludrocortisone (50 μg tablet per nasogastric tube or orally daily) for 7 days
Activated protein C infusion (24 μg/kg/hour for 96 hours) decreases mortality, improves organ dysfunction, and decreases biomarkers of inflammation and coagulation in severe sepsis and septic shock.] Activated protein C is approved for patients who have severe sepsis and a high risk of death,
Activated protein C should not be used in surgical patients who have severe sepsis. By comparison, activated protein C is not beneficial in low-risk patients
RELEVANT RANDOMIZED CONTROLLED TRIALS IN SEVERE SEPSIS, SEPTIC SHOCK, AND ACUTE LUNG INJURY Intervention Mortality (%)[*] Control Mortality (%)[*] NN T[ ] 31 40 11 Patient Group Intervention Control ALI/ARDS[ ][2] Low tidal volume (6 ml/kg) High tidal volume (12 ml/kg) Sepsis and septic shock[1] Early goalusual directed therapy therapy 33 49 6 Severe sepsis and septic shock[3] Activated protein C Placebo 25 31 16 Severe sepsis and septic shock at increased risk of death[ ][3] Activated protein C Placebo 31 44 7.7 Septic shock[8] Hydrocortisone and fludrocortisone Placebo ] ] 10
Controversial Therapies in Septic Shock Vasopressin Deficiency and Use of Vasopressin Hyperglycemia and Intensive Insulin Therapy Renal Dysfunction and Dialysis Low-dose dopamine (2 to 4 μg/kg/minute)
Vasopressin selectively dilates renal afferent but not efferent glomerular arterioles, as well as pulmonary, cerebral, and coronary arterioles. Low-dose vasopressin infusion (0.03 to 0.04 U/minute) increases blood pressure, urine output, and creatinine clearance while dramatically decreasing the doses of norepinephrine required to maintain blood pressure in patients with septic shock.
Low-dose dopamine (2 to 4 μg/kg/minute) does not decrease the need for renal support, does not improve outcomes, and is not recommended
Deep venous thrombosis prophylaxis using low-dose heparin, which may be administered in combination with activated protein C, is recommended for patients who do not have active bleeding, coagulopathy, or a contraindication to heparin
Stress ulcer prophylaxis using H2-receptor antagonists decreases the risk of gastrointestinal hemorrhage. Proton pump inhibitors may also be effective, but they have not been as fully evaluated in septic shock.
Enteral nutrition is generally safer and more effective than total parenteral nutrition, but total parenteral nutrition is sometimes required in patients who have had abdominal sepsis, surgery, or trauma. The use of sedation, neuromuscular blocking agents, and corticosteroids should be minimized because they can exacerbate septic encephalopathy and the polyneuropathy/myopathy of sepsis. Neutropenic patients may benefit from granulocyte colony-stimulating factor
The risk of nosocomial infection is decreased by narrow spectrum antibiotics, early weaning from ventilation, and periodic removal and replacement of catheters
ANTIBIOTICS FOR PATIENTS WHO HAVE SEPTIC SHOCK Source of Sepsis Communityacquired pneumonia Initial Antibiotic Regimen Alternative Antibiotic Regimen Third-generation cephalosporin: cefotaxime 2 g IV q6h; Piperacillin-tazobactam (3.375 ceftriaxone 2 g IV q12h; ceftizoxime 2 g IV q8h) g IV q6h) PLUS PLUS Fluoroquinolone (e.g., ciprofloxacin 400 mg IV q12h; levofloxacin 750 mg IV q24h; moxifloxacin 400 mg IV q24h) OR Fluoroquinolone OR Macrolide Macrolide (e.g., azithromycin 500 mg IV q24h) Hospitalacquired pneumonia Imipenem (0.5 g IV q6h) OR Meropenem (1 g IV q8h) Fluoroquinolone (ciprofloxacin 400 mg IV q12h) PLUS Vancomycin (1.5 g IV q12h) OR Piperacillin/tazobactam (3.375 g IV q6h) PLUS Tobramycin (1.5 mg/kg q8h) PLUS Vancomycin
Abdominal (mixed aerobic/anae robic) Piperacillin/tazobactam (3.375 g IV q6h) OR Ampicillin (2 g IV q4h) PLUS Imipenem (0.5 g IV q6h) (or meropenem 1 g IV q8h) Metronidazole (500 mg IV q8h) PLUS Fluoroquinolone (ciprofloxacin 400 mg IV q12h) Urinary tract Fluoroquinolone (ciprofloxacin 400 mg IV q12h) Ampicillin (2 g IV q4h) PLUS Gentamicin (1.5 mg/kg IV q8h) OR Third-generation cephalosporin (cefotaxime 2 g IV q6h; OR ceftriaxone 2 g IV q12h; OR ceftizoxime 2 g IV q8h) Necrotizing fasciitis Imipenem (0.5 g IV q6h) Penicillin G (if confirmed group A streptococci)
Primary bacteremia (normal host) Piperacillin/tazobactam (3.375 g IV q6h) PLUS Imipenem (0.5 g IV q6h) PLUS Vancomycin (1.5 g IV q12h) Vancomycin (1.5 g IV q12h) Primary bacteremia (intravenous drug user) Cellulitis Vancomycin (1.5 g IV q12h) PLUS Piperacillin/tazobactam (3.375 g IV q6h) PLUS Fluoroquinolone (e.g., ciprofloxacin 400 mg IV q12h) Vancomycin (1.5 g IV q12h) Ciprofloxacin (400 mg IV q12h) PLUS Imipenem (0.5 g IV q6h) Clindamycin (900 mg IV q8h)
Febrile neutropenia Cefepime (2 g IV q8h) PLUS Piperacillin/tazobactam (3.375 g IV q6h) PLUS Vancomycin (1.5 g IV q12h) Gentamicin (1.5 mg/kg q8h) OR Imipenem (0.5 g IV q6h) PLUS Gentamicin (1.5 mg/kg q8h) Bacterial meningitis Ceftriaxone (2 g IV q12h) PLUS Gram-positive cocci: Vancomycin PLUS Ampicillin (3 g IV q6h) PLUS Ceftriaxone (2 g IV q12h) Vancomycin (1.5 g IV q12h) PLUS Gram-negative diplococci: Cefotaxime (2 g IV q4 6h) Dexamethasone (0.15 mg/kg IV q6h for 2 4 days) Gram-positive bacilli: Ampicillin (3 g IV q6h) PLUS Gentamicin Gram-negative bacilli: Ceftazidime (2 g IV q8h) PLUS Gentamicin (1.5 mg/kg IV q8h) All above PLUS Dexamethasone
Prognosis The 28-day mortality rate of septic shock is 40 to 70%. Early deaths (in the first 72 hours) are usually the result of refractory, progressive shock despite escalating life support.
The number of dysfunctional organs and the progression or lack of improvement of organ dysfunction are indicators of increased risk of death
Good luck