TY - CHAP M1 - Book, Section TI - Use of Vasopressors and Inotropes in the Pharmacotherapy of Shock A1 - Maclaren, Robert A1 - Mueller, Scott W. A1 - Dasta, Joseph F. A2 - DiPiro, Joseph T. A2 - Talbert, Robert L. A2 - Yee, Gary C. A2 - Matzke, Gary R. A2 - Wells, Barbara G. A2 - Posey, L. Michael PY - 2017 T2 - Pharmacotherapy: A Pathophysiologic Approach, 10e AB - KEY CONCEPTS Continuous hemodynamic monitoring with an arterial catheter and/or a central venous catheter should be used early and throughout the course of septic shock to assess mean arterial pressure (MAP), intravascular fluid status and arterial and venous oxygenation and monitor response to therapies. They can be used for monitoring the response to drug therapy and guiding dosage titration. Lactate production is increased under anaerobic conditions. Mixed venous oxygen saturation (Svo2) or central venous oxygen saturation (Scvo2) are indicative of tissue perfusion. Elevated serum lactate concentrations or low Svo2/Scvo2 represent global perfusion abnormalities. Lactate clearance or Svo2/Scvo2 may be used to assess repayment of oxygen to the tissues. Gastrointestinal tonometry and sublingual capnometry represent methods of assessing regional perfusion but are used infrequently. Early goal-directed therapy with aggressive fluid resuscitation within the first 6 hours of presentation improves survival of patients with sepsis and septic shock. Goals of therapy with vasopressors and inotropes in septic shock should be predetermined and should optimize global and regional perfusion parameters (eg, 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), MAP more than or equal to 65 mm Hg, urine production more than or equal to 0.5, mL/kg/h, and either lactate clearance of more than or equal to 20% or Svo2 more than or equal to 65% or Scvo2 more than or equal to 70%. 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. 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. 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 (eg, 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, and other hemodynamic variables. 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. First-line therapy of septic shock is aggressive volume resuscitation with crystalloid ... SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accesspharmacy.mhmedical.com/content.aspx?aid=1145179598 ER -