Septic shock is also caused by profound vasodilation but specifically from substances released into the circulating blood by infective agents. One of the most common is endotoxin, a lipopolysaccharide released from bacteria. This substance induces the formation of a nitric oxide synthase (called inducible nitric oxide synthase to distinguish it from the normally present constitutive nitric oxide synthase) in endothelial cells, vascular smooth muscle, and macrophages that then produce large amounts of the potent vasodilator nitric oxide. The termdistributive shock is sometimes used to describe both the anaphylactic and septic shock states.







Septic shock is a clinical syndrome associated with severe infection and is characterized by a systemic inflammatory response with resultant tissue injury.1 The following definitions have been established by a consensus conference convened by the

  • Systemic inflammatory response syndrome (two or more of the following):
  • Temperature > 38°C or < 36°C
  • Heart rate > 90 beats/min
  • Respiratory rate > 20 breaths/min or PCO2 < 32 mmHg
  • WBC > 12,000/μL or < 4000/μL
  • Sepsis: Infection with a systemic inflammatory response
  • Severe sepsis: Sepsis with organ dysfunction
  • Septic Shock: Acute circulatory failure with persistent unexplained hypotension




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Initial Resuscitation: Begin as soon as the syndrome is recognized. Do not wait for ICU admission.1 Goals for the first 6 h of resuscitation include:

  • CVP 8–12 mm Hg
  • MAP ≥ 65 mm Hg
  • Urine output ≥ 0.5 mL/kg/h
  • Central venous or Sv̄O2 ≥ 70%
  • If the S¯VO2 goal is not achieved with fluid resuscitation to the target CVP within the first 6 h, add transfusion of PRBC to a hematocrit of ≥ 30%, infusion of dobutamine, or both.

Diagnosis: Obtain cultures before initiating antibiotic therapy. Draw blood cultures peripherally, and from each vascular access device. Obtain appropriate imaging studies to evaluate for possible sources when possible. Remember: transport of a critically ill patient can be dangerous.

Antibiotic Therapy: Obtain cultures and initiate IV antibiotics within the first hour after recognizing severe sepsis. Consider broad-spectrum antibiotics on the basis of susceptibility patterns at the hospital. Alter antibiotics as dictated by culture results, or discontinue them if a noninfectious cause of cardiovascular collapse is identified.

Source Control: Evaluate for possible source control measures (eg, abscess drainage, debridement, removal of infected devices). Expedite source control after initial resuscitation.

Fluid Therapy: No evidence-based support exists to guide choice of resuscitation fluid (natural or artificial colloid vs isotonic crystalloid). Give fluid challenges as a bolus with careful monitoring so that hemodynamic response can be observed. Large volumes may be needed during the first 24 h of management.

Vasopressors: If fluid resuscitation does not restore adequate blood pressure and perfusion, initiate vasopressor support with dopamine or norepinephrine via a central venous catheter. Do not use “renal dose” dopamine as a protective strategy because it has no demonstrated outcome benefit. Direct measure of arterial blood pressure with arterial catheters is preferred over cuff measurements in the setting of shock. Add low-dose vasopressin (0.01–0.04 units/min) if shock is refractory to fluid resuscitation and usual vasopressor support.

Inotropic Therapy: If CO stays low despite fluid resuscitation, add dobutamine with the goal of achieving adequate O2 delivery to peripheral tissues. If hypotension is present, use dobutamine in conjunction with vasopressors (ie, norepinephrine).

Steroids:Hydrocortisone is recommended for patients with septic shock necessitating vasopressor support (200–300 mg/d in divided doses or by continuous infusion). Higher doses are not effective and are potentially harmful. Relative adrenal insufficiency has been defined as a post-ACTH (250 mcg stimulation test) cortisol increase < 9 mcg/dL at 30–60 min. Some clinicians would discontinue steroid therapy in patients who respond appropriately to the stimulation test.

Recombinant Human Activated Protein C: Consider rhAPC (Xigris) for patients at high risk of death (APACHE II score ≥ 25, multiple organ system dysfunction, septic shock, sepsis-induced ARDS). Carefully review contraindications before starting this therapy.

Blood Product Administration: After resolution of the shock state (and in the absence of ongoing hemorrhage, coronary artery disease, etc), decrease the transfusion threshold to 7 g/dL for most patients with a target hemoglobin of 7–9 g/dL. Erythropoietin is not recommended for management of anemia associated with sepsis in the absence of other indications (eg, renal failure). FFP is not recommended for the correction of abnormal clotting times unless bleeding is present or an invasive procedure anticipated. Administration of antithrombin is not recommended. Transfuse platelets when the platelet count decreases to < 5000/μL, and consider transfusion for platelet counts of 5000–30,000/μL if there is high risk of hemorrhage.

Mechanical Ventilation of Sepsis-Induced Acute Lung Injury: The Surviving Sepsis Guidelines support the low tidal volume (6 mL/kg) strategy (ie, ARDSNet) with goal plateau pressures < 30 cm water. Permissive hypercapnia is allowed if needed; PEEP is adjusted on the basis of FIO2 requirement or is titrated to achieve optimal compliance. Consider prone positioning of patients who need high FIO2. Elevate the head of bed to 45 degrees to reduce pneumonia risk.

Sedation, Analgesia, and Neuromuscular Blockade in Sepsis: Sedation protocols (with scales such as the RASS) and daily interruption of sedation have been shown to decrease duration of mechanical ventilation and hospital length of stay. Avoid neuromuscular blockade unless absolutely necessary.

Glucose Control: Recommended upper limit for glucose control is 150 mg/dL. (The range used in the landmark study [N Engl J Med 2001;345:1359–1367] of intensive insulin therapy in critically ill patients was 80–110 mg/dL). Extending the upper range of glucose control reduces hypoglycemic episodes. Tight glucose control is achieved through infusion of insulin. Assure a glucose source (eg, D5 or D10 infusion). Enteral feeding is the preferred source of glucose.

Renal Replacement: If the patient is in hemodynamically stable condition, continuous venovenous hemofiltration (CVVH) and intermittent hemodialysis are equivalent therapies. CVVH is more appropriate for hemodynamically unstable patients.

Bicarbonate Therapy: Bicarbonate therapy is not recommended for the management of sepsis-related lactic acidemia for pH ≥ 7.15.

Deep Vein Thrombosis Prophylaxis: Administer DVT prophylaxis in the form of subcutaneous heparin or low-molecular-weight heparin. If contraindications are present, consider mechanical prophylaxis sequential compression devices).

Stress Ulcer Prophylaxis: H2-receptor inhibitors are preferred.

Consideration for Limitation of Support: Communication between caregivers and families is vital, particularly with respect to end of life care and patient wishes.

Pediatric Considerations: In general, the aforementioned guidelines apply to adult patients. Refer to the Surviving Sepsis Campaign guidelines for special issues related to the care of pediatric patients (Crit Care Med 2004;32[11 suppl]).



Complications of Injecting Drug Use

  • Local problems—Abscess (Figures 240-2 
    Image not available.

    A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of ­Richard P. Usatine, MD.)

    and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2
    • IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
    • Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
  • IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
    • Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.


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A 75-year-old triathlete complains of gradually worsening vision over the past year. It seems to be involving near and far vision. The patient has never required corrective lenses and has no significant medical history other than diet-controlled hypertension. He takes no regular medications. Physical examination is normal except for bilateral visual acuity of 20/100. There are no focal visual field defects and no redness of the eyes or eyelids. Which of the following is the most likely diagnosis?

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The correct answer is A. You answered A.

Age-related macular degeneration is a major cause of painless, gradual bilateral central visual loss. It occurs as nonexudative (dry) or exudative (wet) forms. Recent genetic data have shown an association with the alternative complement pathway gene for complement factor H. The mechanism link for that association is unknown. The nonexudative form is associated with retinal drusen that leads to retinal atrophy. Treatment with vitamin C, vitamin E, beta-carotene, and zinc may retard the visual loss. Exudative macular degeneration, which is less common, is caused by neovascular proliferation and leakage of choroidal blood vessels. Acute visual loss may occur because of bleeding. Exudative macular degeneration may be treated with intraocular injection of a vascular endothelial growth factor antagonist (bevacizumab or ranibizumab). Blepharitis is inflammation of the eyelids usually related to acne rosacea, seborrheic dermatitis, or staphylococcal infection. Diabetic retinopathy, now a leading cause of blindness in the United States, causes gradual bilateral visual loss in patients with long-standing diabetes. Retinal detachment is usually unilateral and causes visual loss and an afferent pupillary defect.


Mr. Jenson is a 40-year-old man with a congenital bicuspid aortic valve who you have been seeing for more than a decade. You obtain an echocardiogram every other year to follow the progression of his disease knowing that bicuspid valves often develop stenosis or regurgitation requiring replacement in middle age. Given his specific congenital abnormality, what other anatomic structure is important to follow on his biannual echocardiograms?

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The correct answer is A. You answered A.

The answer is A. (Chap. 282) Bicuspid aortic valve is among the most common of congenital heart cardiac abnormalities. Valvular function is often normal in early life and thus may escape detection. Due to abnormal flow dynamics through the bicuspid aortic valve, the valve leaflets can become rigid and fibrosed, leading to either stenosis or regurgitation. However, pathology in patients with bicuspid aortic valve is not limited to the valve alone. The ascending aorta is often dilated, misnamed “poststenotic” dilatation; this is due to histologic abnormalities of the aortic media and may result in aortic dissection. It is important to screen specifically for aortopathy because dissection is a common cause of sudden death in these patients.



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