MAINTAIN ADEQUATE CENTRAL VENOUS PRESSURE
Corresponding Bundle Element
In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/L (36 mg/dL) achieve central venous pressure (CVP) of > 8 mm Hg.
Central Venous Pressure Goal Related Measures
Background
Goal-directed therapy represents an attempt to predefine resuscitation end points to help clinicians at the bedside to resuscitate patients in septic shock. The end points used vary according to the clinical study but attempt to adjust cardiac preload, contractility, and afterload to balance systemic oxygen delivery with demand.
Two essential features of early goal-directed therapy include: 1) maintaining an adequate central venous pressure (CVP) to carry out other hemodynamic adjustments; and 2) maximizing mixed or central venous oxygen saturation, discussed elsewhere.
Following the Sepsis Resuscitation Bundle, once lactate is > 4 mmol/L (36 mg/dL), or hypotension has been demonstrated to be refractive to an initial fluid challenge with 20 mL/kg of crystalloid or colloid equivalent, patients should then have their CVP maintained > 8 mm Hg.
Of note, in adhering to this strategy, patients receive the initial minimum 20 mL/kg fluid challenge prior to placement of a central venous catheter and attempts to maximize CVP. This recommendation is consistent with the methods used in Rivers et al. (1)
Maintaining CVP
Techniques to maintain an appropriate CVP amount to placing a central venous catheter and delivering repeated fluid challenges until the target value is achieved. Fluid challenges are distinct from an increase in the rate of maintenance fluid administration (see Treat Hypotension and Elevated Lactate First with Fluids).
Consider Blood Products
In carrying out early goal-directed therapy, one key aim is central venous pressure, but it is also imperative to maintain central or mixed venous oxygen saturation targets. If a patient is both hypovolemic and anemic with a hematocrit less than 30 percent of blood volume, it is appropriate to transfuse packed red blood cells. This may have the dual advantage of increasing oxygen delivery to ischemic tissue beds and keeping central venous pressure > 8 mm Hg for longer periods than fluids alone.
Special Considerations
In mechanically ventilated patients, a higher target central venous pressure of 12 to 15 mm Hg is recommended to account for the presence of positive end expiratory pressure and increases in intrathoracic pressure.
Similar consideration to the above may be warranted in circumstances of increased abdominal pressure.
Although the cause of tachycardia in septic patients may be multifactorial, a decrease in elevated pulse with fluid resuscitation is often a useful marker of improving intravascular filling.
Rivers Protocol
Rivers et al. performed a randomized, controlled, predominantly blinded study in an 850-bed tertiary referral center over a 3-year period. This study was performed in the emergency department of the hospital and enrolled patients presenting with severe sepsis or septic shock who fulfilled two of the four systemic inflammatory response syndrome criteria in association with a systolic blood pressure of < 90 mm Hg after a 20–30 mL/kg crystalloid challenge or a blood lactate concentration of > 4 mmol/L (36 g/dL).
The patients were randomized to receive six hours of standard therapy or six hours of early goal-directed therapy before admission to the intensive care unit. Clinicians who were subsequently involved in the care of these patients were blinded to the treatment arm of the study.
The control group’s care was directed according to a protocol for hemodynamic support. The aims of this protocol were to ensure that the patients had a central venous pressure of between 8 and 12 mm Hg, a mean arterial pressure of > 65 mm Hg, and a urine output of > 0.5 mL·kg-1·min-1. These goals were targeted with the use of 500-mL boluses of crystalloid or colloid and vasopressor agents as necessary. The patients assigned to the early goal-directed therapy group received a central venous catheter capable of measuring ScvO2. Their treatment aims were then the same as the control groups, except that they also had to achieve a ScvO2 of > 70 percent.
The patients assigned to the early goal-directed therapy group received a central venous catheter capable of measuring ScvO2. Their treatment aims were then the same as the control groups, except that they also had to achieve a ScvO2 of > 70 percent. This was achieved first by the administration of transfused red blood cells, then with positive inotropic therapy, and if this goal was then not achieved, by sedation and mechanical ventilation to reduce oxygen demand.
The study enrolled 263 patients equally between the two groups. There were no significant differences between the two groups at baseline. During the initial 6 hours of therapy, the early goal-directed therapy group received more intravenous fluid (5.0 vs 3.5 L, p < .001), red cell transfusions (p < .001), and inotropic therapy (p < .001). During the subsequent 66 hours, the control group received more red cell transfusions (p < .001), more vasopressors (p = .03), and had a greater requirement for mechanical ventilation (p < .001) and pulmonary artery catheterization (p = .04). This in part reflects the fact that the control group patients were relatively under-resuscitated initially, and this was noticed and thus acted on by clinicians later on in their treatment course. In-hospital mortality was significantly higher in the control group than in the early goal-directed therapy group (46.5 percent vs. 30.5 percent, p = .009). These differences were maintained through to 28 (p = .01) and 60 days (p = .03).
Grading the Evidence
1. The Surviving Sepsis Campaign recommends the protocolized resuscitation of a patient with sepsis-induced shock, defined as tissue hypoperfusion (hypotension persisting after initial fluid challenge or blood lactate concentration equal to or greater than 4 mmol/L). This protocol should be initiated as soon as hypoperfusion is recognized and should not be delayed pending ICU admission. During the first 6 hours of resuscitation, the goals of initial resuscitation of sepsis-induced hypoperfusion should include all of the following as one part of a treatment protocol:
- Central venous pressure (CVP): 8-12 mm Hg
- Mean arterial pressure (MAP) ≥ 65 mm Hg
- Urine output ≥ 0.5 mL·kg-1·min-1
- Central venous (superior vena cava) or mixed venous oxygen saturation ≥ 70% or > 65%, respectively (Grade 1C)
Rationale. Early goal-directed resuscitation has been shown to improve survival for emergency department patients presenting with septic shock in a randomized, controlled, single-center study (1). Resuscitation directed toward the previously mentioned goals for the initial 6-hr period of the resuscitation was able to reduce 28-day mortality rate. The consensus panel judged use of central venous and mixed venous oxygen saturation targets to be equivalent. Either intermittent or continuous measurements of oxygen saturation were judged to be acceptable. Although blood lactate concentration may lack precision as a measure of tissue metabolic status, elevated levels in sepsis support aggressive resuscitation. In mechanically ventilated patients or patients with known pre-existing decreased ventricular compliance, a higher target CVP of 12-15 mm Hg is recommended to account for the impediment to filling (2). Similar consideration may be warranted in circumstances of increased abdominal pressure or diastolic dysfunction (3). Elevated central venous pressures may also be seen with pre-existing clinically significant pulmonary artery hypertension. Although the cause of tachycardia in septic patients may be multifactorial, a decrease in elevated pulse rate with fluid resuscitation is often a useful marker of improving intravascular filling. Recently published observational studies have demonstrated an association between good clinical outcome in septic shock and MAP > 65 mm Hg as well as central venous oxygen saturation (ScvO2, measured in superior vena cava, either intermittently or continuously) of > 70% (4). Many recent studies support the value of early protocolized resuscitation in severe sepsis and sepsis-induced tissue hypoperfusion (5-10). Studies of patients with shock indicate that SvO2 runs 5% to 7% lower than central venous oxygen saturation (ScvO2) (11) and that an early goal-directed resuscitation protocol can be established in a non-research general practice venue (12).
There are recognized limitations to ventricular filling pressure estimates as surrogates for fluid resuscitation (13,14). However, measurement of CVP is currently the most readily obtainable target for fluid resuscitation. There may be advantages to targeting fluid resuscitation to flow and perhaps to volumetric indices (and even to microcirculation changes) (15-18). Technologies currently exist that allow measurement of flow at the bedside (19,20).
The above category 1 recommendations are strong recommendations for care based on a number of qualitative considerations. “B” level evidence generally derives from randomized control trials with certain limitations or very well-done observational or cohort studies. “C” level evidence reflects well-done observational or cohort studies with controls. “D” level evidence generally reflects case series data or expert opinion.
2. The Surviving Sepsis Campaign suggests that during the first 6 hrs of resuscitation of severe sepsis or septic shock, if SCVO2 or SvO2 of 70% or 65% respectively is not achieved with fluid resuscitation to the CVP target, then transfusion of packed red blood cells to achieve a hematocrit of ≥ 30% and/or administration of a dobutamine infusion (up to a maximum of 20 μg·kg-1·min-1) be utilized to achieve this goal (Grade 2C).
Rationale. The protocol used in the study cited previously targeted an increase in ScvO2 to ≥ 70% (1). This was achieved by sequential institution of initial fluid resuscitation, then packed red blood cells, and then dobutamine. This protocol was associated with an improvement in survival. Based on bedside clinical assessment and personal preference, a clinician may deem either blood transfusion (if Hct is less than 30%) or dobutamine the best initial choice to increase oxygen delivery and thereby elevate ScvO2. When fluid resuscitation is believed to be already adequate. The design of the aforementioned trial did not allow assessment of the relative contribution of these two components(i.e., increasing O2 content or increasing cardiac output) of the protocol on achievement of improved outcome.
The above category 2 suggestion is a weaker recommendation for care based on a number of qualitative considerations. “B” level evidence generally derives from randomized control trials with certain limitations or very well-done observational or cohort studies. “C” level evidence reflects well-done observational or cohort studies with controls. “D” level evidence generally reflects case series data or expert opinion.
Tips
1. Create a standardized protocol that includes a goal CVP > 8 mm Hg for patients with lactate > 4 mmol/L or hypotension not responding to initial fluid resuscitation (septic shock).
2. Stress the importance of prioritization: initial fluid challenge as defined, followed by central line placement, followed by assessment of CVP; if CVP is low, the addition of PRBCs is appropriate if hematocrit is less than 30% and MAP remains < 65 mg Hg, followed by further fluid challenges to keep CVP > 8 mm Hg.
3. If your emergency department does not commonly perform these techniques, provide in-service training to emergency department personnel regarding CVP monitoring and the importance of leveling equipment relative to the patient’s heart.
4. Do not wait for transfer to the ICU to initiate CVP monitoring.
References
1. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–1377
2. Bendjelid K, Romand JA: Fluid responsiveness in mechanically ventilated patients: A review of indices used in intensive care. Intensive Care Med. 2003; 29:352–360
3. Malbrain ML, Deeren D, De Potter TJ: Intra-abdominal hypertension in the critically ill: It is time to pay attention. Curr Opin Crit Care. 2005; 11:156-171
4. Varpula M, Tallgren M, Saukkonen K, et al: Hemodynamic variables related to outcome in septic shock. Intensive Care Med. 2005; 31:1066-1071
5. Kortgen A, Niederprum P, Bauer M: Implementation of an evidence-based “standard operating procedure” and outcome in septic shock. Crit Care Med. 2006; 34(4):943-949
6. Sebat F, Johnson D, Musthafa AA, et al: A multidisciplinary community hospital program for early and rapid resuscitation of shock in nontrauma patients. Chest. 2005; 127(5):1729-1743
7. Shapiro NI, Howell MD, Talmor D, et al: Implementation and outcomes of the Multiple Urgent Sepsis Therapies (MUST) protocol. Crit Care Med. 2006; 34(4):1025-1032
8. Micek SST, Roubinian N, Heuring T, et al: Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med. 2006; 34(11):2707-2713
9. Nguyen HB, Corbett SW, Steele R, et al: Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med. 2007;35(4):1105-1112
10. Shorr AF, Micek ST, Jackson WL, Jr., et al: Economic implications of an evidence-based sepsis protocol: can we improve outcomes and lower costs? Crit Care Med. 2007; 35(5):1257-1262
11. Reinhart K, Kuhn HJ, Hartog C, Bredle DL: Continuous central venous and pulmonary artery oxygen saturation monitoring in the critically ill. Intensive Care Med. 2004; 30:1572-1578
12. Trzeciak S, Dellinger RP, Abate N, et al. Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. Chest. 2006; 129:225-232
13. Magder S. Central venous pressure: A useful but not so simple measurement. Crit Care Med. 2006; 34(8):2224-2227
14. Bendjelid K. Right arterial pressure: Determinant or result of change in venous return? Chest. 2005; 128:3639-3640
15. Vincent JL, Weil MH. Fluid challenge revisited. Crit Care Med. 2006; 34:1333-1337
16. Trzeciak S, Dellinger RP, Parrillo JE, et al. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: Relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med. 2007; 49:88-98
17. De Backer D, Creteur J, Dubois MJ, et al. The effects of dobutamine on microcirculatory alternations in patients with septic shock are independent of its systemic effects. Crit Care Med. 2006; 34:403-408
18. Buwalda M, Ince C. Opening the microcirculation: Can vasodilators be useful in sepsis? Intensive Care Med 2002; 28:1208-1217
19. Boldt J. Clinical review; hemodynamic monitoring in the intensive care unit. Crit Care. 2002; 6:52-59
20. Pinsky MR, Payen D. Functional hemodynamic monitoring. Crit Care. 2005; 9:566-572
21.
Content adapted extensively from
• Dellinger, RP, Levy, MM, Carlet, JM, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008; [published correction appears in Crit Care Med. 2008; 36:1394-1396] 36:296-327
• Rhodes A, Bennett ED. Early goal-directed therapy: An evidence-based review. Crit Care Med. 2004;32(Suppl.):S448 –S450.