Early goal-directed therapy: on terminal life support?

Early goal-directed therapy (EGDT) has become regarded as the standard of care for the management of patients with severe sepsis and septic shock. The elements of EGDT have been bundled together as the “Sepsis Bundle,” and compliance with the elements of the bundle is frequently used as an indicator of the quality of care delivered. The major elements of EGDT include fluid resuscitation to achieve a central venous pressure of 8 to 12 cm of water, followed by the transfusion of packed red cells or an inotropic agent to maintain the central venous oxygen saturation higher than 70%. Although the concept of early resuscitation is a scientifically sound concept, we believe that the major elements of the sepsis bundle are fatally flawed.     

Early goal-directed therapy: what do we do now?

The meta-analysis of early goal-directed therapy (EGDT) by Gu and colleagues in the previous issue of Critical Care adds to the ongoing controversy about the value of EGDT for resuscitating patients with severe sepsis and septic shock. The results of the ProCESS (protocolized care for early septic shock) and ARISE (Australasian resuscitation in sepsis evaluation) trials failed to demonstrate any benefit of EGDT or protocolized resuscitation when compared with ‘usual care’. The questions are the following: What is ‘usual’ care? What is ‘real world’ care? Do the results of a robust and well-conducted randomized controlled trial - in which many patients may be excluded for a variety of reasons - reflect the care given to patients on a daily basis in our emergency departments and intensive care units? Of course, there are no obvious answers to these questions, and many clinicians look forward to managing these patients without protocols. For now, the data do seem to support the management of patients with septic shock without mandated central lines or protocols. Does this mean we should go back to the era of ‘do whatever you want’? No consensus exists among clinicians regarding optimal hemodynamic monitoring, and to date no method has been proven to be superior. Given the amount of fluids given prior to randomization in the ProCESS and ARISE trials, ‘usual care’ appears to now include aggressive, early fluid resuscitation with at least 20 mL/kg of crystalloid and rapid administration of appropriate antibiotics. Certainly, this reflects the impact of the original trial by Rivers and colleagues and the broad-based implementation of the Surviving Sepsis Campaign Guidelines and bundles. If this continues to define ‘usual care’, then perhaps it is no longer necessary to mandate specific protocols for resuscitation, as it appears that standard sepsis management has evolved to be consistent with published protocols.     

Inotropes in goal-directed therapy: Do we need 'goals'?

There is substantial evidence to demonstrate the benefits of goal-directed hemodynamic optimization using fluid loading or inotropic support or both to improve outcome during major surgery. However, until now, only limited pathophysiological data have been available to explain this benefit. The maintenance of adequate tissue perfusion and global oxygen delivery is an essential goal for therapy. In an interesting study, Jhanji and colleagues provided additional data that emphasize the roles of optimization of intravascular fluid status and low doses of inotropes to improve microvascular blood flow and tissue oxygenation. This commentary aims to highlight some issues raised by this important study and provides additional elements to further position these results.     

Tackling the economic burden of postsurgical complications: would perioperative goal-directed fluid therapy help?

Introduction

Pay-for-performance programs and economic constraints call for solutions to improve the quality of health care without increasing costs. Many studies have shown decreased morbidity in major surgery when perioperative goal directed fluid therapy (GDFT) is used. We assessed the clinical and economic burden of postsurgical complications in the University HealthSystem Consortium (UHC) in order to predict potential savings with GDFT.

Methods

Data from adults who had a major surgical procedure in 2011 were screened in the UHC database. Thirteen post-surgical complications were tabulated. In-hospital mortality, hospital length of stay and costs from patients with and without complications were compared. The risk ratios reported by the most recent meta-analysis were used to estimate the potential reduction in post-surgical morbidity with GDFT. Potential cost-savings were calculated from the actual and anticipated morbidity rates.

Results

A total of 75,140 patients met the search criteria, and 8,421 patients developed one or more post-surgical complications (morbidity rate 11.2%). In patients with and without complications, in-hospital mortality was 12.4% and 1.4% (P <0.001), mean hospital length of stay was 20.5 ± 20.1 days and 8.1 ± 7.1 days (P <0.001) and mean direct costs were $47,284 ± 49,170 and $17,408 ± 15,612 (P <0.001), respectively. With GDFT, morbidity rate was projected to decrease to 8.0 - 9.3%, yielding gross costs savings of $43 M - $73 M for the study population or $569 - $970 per patient.

Conclusion

Postsurgical complications have a dramatic impact (+172%) on costs. Potential costs savings resulting from GDFT are substantial. Perioperative GDFT may be recommended not only to improve quality of care but also to decrease costs.     

Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock?

Objective  To test the hypothesis that, in resuscitated septic shock patients, central venous-to-arterial carbon dioxide difference [P(cv-a)CO₂] may serve as a global index of tissue perfusion when the central venous oxygen saturation (ScvO₂) goal value has already been reached. Design  Prospective observational study. Setting  A 22-bed intensive care unit (ICU). Patients  After early resuscitation in the emergency unit, 50 consecutive septic shock patients with ScvO₂ > 70% were included immediately after their admission into the ICU (T0). Patients were separated in Low P(cv-a)CO₂ group (Low gap; n = 26) and High P(cv-a)CO₂ group (High gap; n = 24) according to a threshold of 6 mmHg at T0. Measurements  Measurements were performed every 6 h over 12 h (T0, T6, T12). Results  At T0, there was a significant difference between Low gap patients and High gap patients for cardiac index (CI) (4.3 ± 1.6 vs. 2.7 ± 0.8 l/min/m2, P < 0.0001) but not for ScvO₂ values (78 ± 5 vs. 75 ± 5%, P = 0.07). From T0 to T12, the clearance of lactate was significantly larger for the Low gap group than for the High gap group (P < 0.05) as well as the decrease of SOFA score at T24 (P < 0.01). At T0, T6 and T12, CI and P(cv-a)CO₂ values were inversely correlated (P < 0.0001). Conclusion  In ICU-resuscitated patients, targeting only ScvO₂ may not be sufficient to guide therapy. When the 70% ScvO₂ goal-value is reached, the presence of a P(cv-a)CO₂ larger than 6 mmHg might be a useful tool to identify patients who still remain inadequately resuscitated. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Palivizumab: where to from here?

Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections. In severely immunosuppressed patients RSV can cause significant morbidity and mortality. The only FDA-approved drug for RSV is aerosolized ribavirin. Given the high morbidity and mortality in high-risk populations and inconsistent results with aerosolized ribavirin, new strategies for prevention and treatment of RSV are being sought. Palivizumab is an RSV-specific monoclonal antibody. A randomized, double-blind, placebo-controlled multicenter study showed significant reduction in hospitalization rates among children at high risk of RSV infection who had been given prophylactic palivizumab; these findings led to palivizumab's approval by the FDA in June 1998. Palivizumab also has a role in prevention of severe respiratory tract infections in high-risk infants. In immunocompromised patients, palivizumab has an excellent safety profile and may be beneficial in the prevention and treatment of RSV infections; however, clinical trials are needed to determine its effectiveness. In this article, we review the role of palivizumab in prevention and treatment of RSV infections in immunocompetent and immunocompromised patients.