PANORAMA DEL SECTOR DE INDUSTRIAS CREATIVAS: CASO MANIZALES

Perhaps the leading cause of ICU admission is sepsis. The widespread application of protocolized resuscitation and management has been extensively promoted for more than 10 years by international societies (the Surviving Sepsis campaign [SSC])98,100 _and

has been associated with a marked reduction in sepsis mortality.101-104 _{Data from 171}

ICUs in Australia and New Zealand demonstrated a decline in mortality in patients with septic shock from 40.3% in 2000 to 22% in 2012; at the same time, mortality from sepsis declined from 30.2% to 14.2%.105

Three big randomized controlled trials (RCTs), the Protocolized Care for Early Septic Shock [ProCESS], the Protocolised Management in Sepsis [ProMISe], and the Australasian Resuscitation in Sepsis Evaluation [ARISE], conducted in the United States, United Kingdom, and Australia/New Zealand, respectively,106,107,108 showed no benefit in terms of survival of EGDT109 compared to current usual care, which includes early administration of appropriate antibiotics, volume resuscitation, and source control. Early and appropriate antibiotic administration is critical, as observational studies have shown a relationship between survival and time from sepsis onset to antibiotic administration, in particular in patients with septic shock.110,111 Hypotensive patients who do not receive early resuscitation also have poorer outcomes,110 along with patients where source control is delayed.112,113

With regard to the three large RCTs, what conclusions can be drawn and applied to clinical practice?; first, invasive monitoring and management strategies such as the placement of central venous access should not be routinely applied to all patients with sepsis. It seems reasonable for patients with severe hemodynamic collapse requiring vasopressor support despite volume resuscitation to have a “central line” and potentially central venous pressure (CVP) monitoring although fluid challenges should not be performed based on CVP values alone. Second, along the same lines, therapeutic decisions should not be based on central venous oxygen saturation (ScvO2) alone.

criteria for critically ill patients, as no benefit was observed in patients managed with EGDT, who in aggregate received more transfusions. Along the same lines, the Transfusion Requirements in Septic Shock (TRISS) trial showed no benefit with regard to 90-day mortality (the trial primary outcome) or rates of ischemic events in septic shock patients when a higher hemoglobin threshold for transfusion was used (9 g/dL vs. 7 g/dL).114

What should the target blood pressure be in patients with sepsis?; a large RCT conducted in France, the Sepsis and Mean Arterial Pressure (SEPSISPAM) trial,115 compared blood pressure targets of 65 to 70 mm Hg vs. 80 to 85 mm Hg in patients with septic shock. The overall trial did not show a benefit to higher blood pressure targets, perhaps in part because there was less separation than anticipated of the 2 treatment arms, with those in the standard therapy arm achieving higher blood pressures than expected. However, in a prespecified analysis of patients with chronic hypertension, there was a significant interaction between blood pressure target and renal outcomes. That is, in patients with chronic hypertension, those randomized to the higher blood pressure target had lower rates of doubling SCr (38.9% vs. 50%, p=0.009) and need for RRT over the first 7 study days (31.7% vs. 42.2%, p=0.04). Patients randomized to the higher target blood pressure arm did require vasopressors for longer periods of time and had more atrial fibrillation.

1.4.2. Fluids

Fluid management in patients with sepsis has been extensively studied over the last years. In patients with established AKI, as discussed earlier, SA-AKI is much more complex than decreased renal perfusion; however, improving renal perfusion in the setting of hypotension may help mitigate some of the harmful effects of SA-AKI. Renal blood flow can be estimated as follows: Renal Blood Flow = (MAP – Renal Venous Pressure)/Renal Vascular Resistance.21 _{Although this is probably an oversimplification}

of actual renal blood flow, it conceptualizes the importance of attempting to find the “sweet spot” of “euvolemia” when resuscitating a septic patient; by this, we mean a fluid state in which intravascular volume is optimized with minimal fluid overload. We can see that renal blood flow can be affected by MAP, renal venous pressure, and renal vascular resistance.

It has long been known that hypovolemia produces “pre-renal” ischemic AKI, and the treatment is fluid administration to improve cardiac output and thus oxygen delivery to the kidneys; however, it has become increasingly clear that overzealous fluid administration can cause AKI as well.116,117,118 If the renal venous pressure increases, as it often does when large amounts of fluid are administered, it can lead to decreased renal blood flow and decreased GFR.118 The combination of low MAP and intra-abdominal hypertension (IAH) (which increases renal venous pressure), which are often seen in sepsis, may contribute to SA-AKI. In the surgical literature there is some evidence that EGDT, which is a protocol that tries to maximize cardiac output through fluid and inotrope administration, may decrease incidence of SA-AKI.116 However, the three large sepsis trials previously commented found no benefit with EGDT compared with usual care with regard to mortality or kidney outcomes. 106,107,108

The ADQI had a consensus conference on fluid therapy.119 As part of this conference, a conceptual framework for fluid management was proposed (Fig. 2) that highlights the importance of individualizing fluid resuscitation and the fact that the goals of fluid therapy may vary over the course of disease.120 _{Early on, during the “rescue” phase of}

resuscitation, fluids are needed to improve circulation, as described previously. This is followed by “optimization” and “stabilization” phases in which fluid therapy is titrated to the individual patients. Finally, during the recovery phase, “deescalation” of fluid therapy, which may include diuretics to enhance fluid mobilization, is needed to avoid the sequelae of volume overload.

Figure 2. Patient’s volume status at different stages of resuscitation

In this context, it should be noted that retrospective studies of clinical trials concerning fluid management have suggested that positive fluid balance, but not diuretic administration, is associated with increased mortality in patients with the acute respiratory distress syndrome (ARDS) and early AKI.121 Published recently, three different studies with protocols restricting resuscitation fluids successfully reduced volumes of resuscitation fluids compared with a standard care protocol in adult ICU patients with septic shock.122,123,124