The classes of recommendations (A-E) and levels of evidence (I-V) are defined at the end of the "Major Recommendations" field.
Recommendations for Hemodynamic Support of Septic Patients
Basic Principles
- Resuscitation of patients with sepsis should be initiated expeditiously and pursued vigorously. Measures to improve tissue and organ perfusion are most effective when applied early.
- Patients with septic shock should be treated in an intensive care unit, with continuous electrocardiographic monitoring and monitoring of arterial oxygenation.
- Arterial cannulation should be performed in patients with shock to provide a more accurate measurement of intra-arterial pressure and to allow beat-to-beat analysis so that decisions regarding therapy can be based on immediate and reproducible blood pressure information.
- Resuscitation should be titrated to clinical end points of arterial pressure, heart rate, urine output, skin perfusion, and mental status, and indexes of tissue perfusion such as blood lactate concentrations and mixed venous oxygen saturation.
- Assessment of cardiac filling pressures may require central venous or pulmonary artery catheterization. Pulmonary artery catheterization also allows for assessment of pulmonary artery pressures, cardiac output measurement, and measurement of mixed venous oxygen saturation. Echocardiography may also be useful to assess ventricular volumes and cardiac performance.
Fluid Resuscitation
Recommendation 1 - Level B. Fluid infusion should be the initial step in hemodynamic support of patients with septic shock. Initial fluid resuscitation should be titrated to clinical end points.
Recommendation 2 - Level B. Isotonic crystalloids or iso-oncotic colloids are equally effective when titrated to the same hemodynamic end points.
Recommendation 3 - Level D. Invasive hemodynamic monitoring should be considered in those patients not responding promptly to initial resuscitative efforts. Pulmonary edema may occur as a complication of fluid resuscitation and necessitates monitoring of arterial oxygenation. Fluid infusion should be titrated to a level of filling pressure associated with the greatest increase in cardiac output and stroke volume. For most patients, this will be a pulmonary artery occlusion pressure in the range of 12 to 15 mm Hg. An increase in the variation of arterial pressure with respiration may also be used to identify patients likely to respond to additional fluid administration.
Recommendation 4 - Level C. Hemoglobin concentrations should be maintained between 8 and 10 gm/dL. In patients with low cardiac output, mixed venous oxygen desaturation, lactic acidosis, widened gastric-arterial PCO2 gradients, or significant cardiac or pulmonary disease, transfusion to a higher concentration of hemoglobin may be desirable.
Vasopressor Therapy
Recommendation 1 - Level C. Dopamine and norepinephrine are both effective for increasing arterial blood pressure. It is imperative to ensure that patients are adequately fluid resuscitated. Dopamine raises cardiac output more than norepinephrine, but its use may be limited by tachycardia. Norepinephrine may be a more effective vasopressor in some patients.
Recommendation 2 - Level D. Phenylephrine is an alternative to increase blood pressure, especially in the setting of tachyarrhythmias. Epinephrine can be considered for refractory hypotension, although adverse effects are common, and epinephrine may potentially decrease mesenteric perfusion.
Recommendation 3 - Level B. Administration of low doses of dopamine to maintain renal function is not recommended.
Recommendation 4 - Level C. Patients with hypotension refractory to catecholamine vasopressors may benefit from addition of replacement dose steroids.
Recommendation 5 - Level D. Low doses of vasopressin given after 24 hours as hormone replacement may be effective in raising blood pressure in patients refractory to other vasopressors, although no conclusive data are yet available regarding outcome.
Inotropic Therapy
Recommendation 1 - Level C. Dobutamine is the first choice for patients with low cardiac index and/or low mixed venous oxygen saturation and an adequate mean arterial pressure following fluid resuscitation. Dobutamine may cause hypotension and/or tachycardia in some patients, especially those with decreased filling pressures.
Recommendation 2 - Level B. In patients with evidence of tissue hypoperfusion, addition of dobutamine may be helpful to increase cardiac output and improve organ perfusion. A strategy of routinely increasing cardiac index to predefined "supranormal" levels (>4.5 L·min-1·m-2) has not been shown to improve outcome.
Recommendation 3 - Level C. A vasopressor such as norepinephrine and an inotrope such as dobutamine can be titrated separately to maintain both mean arterial pressure and cardiac output.
Definitions
Level I: Large, randomized trials with clear-cut results; low risk of false-positive (alpha) error or false-negative (beta) error
Level II: Small, randomized trials with uncertain results; moderate to high risk of false-positive (alpha) error and/or false-negative (beta) error
Level III: Nonrandomized, contemporaneous controls
Level IV: Nonrandomized, historical controls and expert opinion
Level V: Case series, uncontrolled studies, and expert opinion
Strength of Recommendations
- Supported by at least two level I investigations
- Supported by only one level I investigation
- Supported by level II investigations only
- Supported by at least one level III investigation
- Supported by level IV or level V investigations only