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  • image Continuous hemodynamic monitoring with an arterial catheter or a central venous catheter capable of measuring mixed venous oxygen saturation (Svo2) or central venous oxygen saturation (Scvo2) should be used early and throughout the course of septic shock to assess intravascular fluid status and ventricular filling pressures, determine cardiac output (CO), and monitor arterial and venous oxygenation. They can be used for monitoring the response to drug therapy and guiding dosage titration.
  • image Early goal-directed therapy with aggressive fluid resuscitation in the emergency department within the first 6 hours of presentation improves survival of patients with sepsis and septic shock.
  • image Lactate production is increased under anaerobic conditions. Elevated serum lactate concentrations represent global perfusion abnormalities. Lactate clearance may be used to assess repayment of oxygen to the tissues. GI tonometry and sublingual capnometry represent methods of assessing regional perfusion but are used infrequently.
  • image Derangements in adrenergic receptor sensitivity or activity frequently result in resistance to catecholamine vasopressor and inotropic therapy in critically ill patients. These changes may be a function of endogenous catecholamine concentrations, dosage/duration of exposure to and type of exogenously administered vasopressors, stage of septic shock, preexisting illness, and other factors.
  • image In refractory septic shock, rational use of vasopressor or inotropic agents should be guided by receptor activity, pharmacologic and pharmacokinetic characteristics, and regional and systemic hemodynamic effects of the drug and should be tailored to the patient’s physiologic needs. Pharmacologically sound combinations of vasopressor and/or inotrope agents should be initiated early to optimize and facilitate rapid response.
  • image Goals of therapy with vasopressors and inotropes should be predetermined and should optimize global and regional perfusion parameters (e.g., cardiac, renal, mesenteric, and periphery) to normalize cellular metabolism. This can be accomplished by continuous or intermittent measurements. Targeted goals should be central venous pressure (CVP) of 8 to 12 mm Hg (up to 15 mm Hg in mechanically ventilated patients, patients with preexisting left ventricular dysfunction, or patients with abdominal distension), mean arterial pressure (MAP) ≥65 mm Hg, Svo2 ≥65% or Scvo2 ≥70%, and lactate clearance of ≥20%.
  • image Dose titration and monitoring of vasopressor and inotropic therapy should be guided by the “best clinical response” while observing for and minimizing evidence of myocardial ischemia (e.g., tachydysrhythmias, electrocardiographic changes, troponin elevation), renal (decreased glomerular filtration rate and/or urine production), splanchnic/gastric (low intramucosal pH, bowel ischemia), or peripheral (cold extremities) hypoperfusion, and worsening of partial pressure of arterial oxygen (Pao2), pulmonary artery occlusive pressure (PAOP), and other hemodynamic variables.
  • image Much higher dosages of all vasopressors and inotropes than traditionally recommended are required to improve hemodynamic and oxygen-transport variables in patients with septic shock. Arbitrarily targeting vasopressor and inotrope therapy to supranormal values of global oxygen-transport variables cannot be recommended because of the lack of clear benefit and possible increased morbidity.
  • image First-line therapy of septic shock is aggressive volume resuscitation with crystalloid or colloid types of fluids. Norepinephrine is the preferred initial vasopressor agent for hemodynamic support. Norepinephrine achieves ...

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