Fluid Resuscitation in Septic Shock

Dr. Perz,

Boyd, J.H., Forbes, J., Nakada, T., Walley, K., Russell, J.A. Fluid Resuscitation in septic shock: A positive fluid balance and elevated central venous pressure are associated with increased mortality. Critical Care Medicine: Volume 39, Issue 2 (Feb 2011).

The objective of this study was to determine when central venous pressure (CVP) and fluid balance after resuscitation for septic shock are associated with mortality by doing a retrospective review of the use of IV fluids during the first 4 days of care.  The study concluded that a more positive fluid balance both early in resuscitation and cumulatively over four days is associated with an increased risk of mortality in septic shock.  CVP may be used to gauge fluid balance <12 hours into septic shock but becomes an unreliable indicated of fluid balance thereafter.  The study referenced a VASST study (Vasopressin in Septic Shock Trial), which noted that optimal survival occurred with a positive fluid balance of approximately 3L at 12 hours.

This study was a retrospective review of 778 patients from the VASST, all of whom were in septic shock and receiving at least 5mcg of norepinephrine per minute; they analyzed whether a positive fluid balance in the first 12 hours of resuscitation and during the next 4 days was associated with an increase in 28-day mortality. Using the Surviving Sepsis guidelines from 2008, the study grouped patients into those who fell into the recommended range (CVP = 8-12), those with CVP < 8 and those with a CVP >12 and analyzed whether a CVP of 8-12 had a survival advantage.  In this VASST, the patients at 12 hours with a CVP <8 had a lower mortality over those with CVPs of 8-12 and those with CVPs >12.  However, the study also concluded that there is a point when too little fluid is also detrimental.  It also concluded that CVP may be useful along with other measures to gauge adequacy of fluid resuscitation <12 hours into septic shock but becomes an unreliable marker of fluid balance thereafter.  Optimal survival in the VASST study occurred with a positive fluid balance of appx. 3L at 12 hours.  

Lactate/Pyruvate as a marker of tissue hypoxia

Dr. Perz

Lactate/Pyruvate Ratio as a Marker of Tissue Hypoxia in Circulatory and Septic Shock

Rimachi, R., Bruzzi de Carvahlo, F., Orellano-Jimenez, C., Cotton, F., Vincents, J.L., De Backer, D.  Anesth Intensive Care 2012; 40:427-423.

                This article described a prospective, observational study which measured arterial lactate and pyruvate concentrations within the first four hours of shock and at four hour intervals during the first 24 hours in 26 patients with septic shock and 13 patients with cardiogenic shock.    The basis for this study is based on the fact that several authors have suggested that lactate in itself may not be an accurate measure of hypoxia.  Increased blood lactate concentrations may also, especially in patients with sepsis, result from impaired clearance of lactate, inhibition of pyruvate dehydrogenase, and accelerated aerobic glycolysis due to the activation of the Na/K ATPase by catecholamines.  These authors suggest that lactate should be measured with pyruvate, to attempt to distinguish between hypoxic and non-hypoxic sources of lactate.  In anaerobic conditions, pyruvate is transformed to lactate and thus, the lactate/pyruvate (L/P) ratio increases.  So, this study attempted to use the L/P ratio to assess the contribution of hypoxic and non-hypoxic causes to hyperlactataemia.

The lactate/pyruvate ratio was measured in each of these patients, and several observations were noted.  Blood lactate values were higher at shock onset and remained higher in the non-survivors in relation to the survivors; the lactate/pyruvate ratio at shoch onset was significantly higher in the non-survivors.  All patients with cardiogenic shock had hyperlactataemia at the onset of shock and 69% had a high lactate/pyruvate ratio, and of the septic shock patients, 65% had hyperlactataemia and 76% had a high lactate/pyruvate ratio.  Eighteen percent of patients died during the first 24 hours, thirty one percent of patients died later in the ICU and fifty four percent were discharged alive from the ICU.  Ultimately, the study concluded that the L/P ratio confirms that hyperlactataemia is frequently, but not solely due to hypoxia, especially at the onset of shock.

Goal Directed Fluid Management During High Risk Surgery, Dr. Perz

Katie Perz, D.O.

Goal Directed Fluid Management Based on Pulse Pressure Variation Monitoring During High Risk Surgery: A Pilot Randomized Controlled Trial

Lopes, M., Oliveira, M., Pereira, V., Lemos, I., Auler, J., Michard, F.  J Crit Care, v.11 (5); 2007.

Several studies have shown that maximizing stroke volume by volume loading during high-risk surgery may improve post operative outcome.  The goal of this study was to determine whether this goal could be achieved by simply by minimizing the variation in arterial pulse pressure induced by mechanical ventilation.  In this study, thirty three patients undergoing high-risk surgery were randomized; the intervention group was continuously monitored during surgery by a multiparameter bedside monitor and minimized to 10% or less by volume loading.  The study was done in Brazil, and the “multiparameter bedside monitor” was made by a company called Dixtal, and the monitor was referred to as the DX2020.  The arterial pressure curve was recorded via a specific module (IBPplus; Dixtal), allowing calculation of the change in pulse pressure.  The study concluded that monitoring and minimizing the change in pulse pressure by fluid loading during high-risk surgery decreases the incidence of post operative complications and also the duration of mechanical ventilation, stay in the ICU, and stay in the hospital.

Changing Paradigms in Surgical Rescuscitation, Dr. Perz

Katie Perz, D.O.

Patients undergoing emergency surgery typically require resuscitation, generally either because they are either hemorrhaging or septic. Intravascular hypovolemia is common at the time of anesthesia and needs to be treated appropriately based on its root cause; fluid resuscitation is different in bleeding and septic patients.  In bleeding patients, it is advisable to maintain a deliberately low blood pressure to facilitate clot formation and stabilization, which is described as controlled hypotension.  If massive transfusion is anticipated, blood products should be administered from the outset to prevent the coagulopathy of trauma.  Early use of plasma in a 1:1 ratio with pRBCs and FFP has been associated with improved outcomes.  In septic patients, early fluid loading is recommended.  The concept of “goal directed resuscitation is based on continuing resuscitation until venous oxygen saturation is normalized.  In either bleeding or septic patients, however, the most important goal remains surgical control of the source of pathology and nothing should delay transfer to the operating room. 

Newer modalities of fluid monitoring are in use, and while they are better than old modalities, they still lack validation.   The previous goal standard was CVP and PA catheters, but these methods of monitoring are falling out of favor and it is questionable whether they affect outcomes at all, or if they could possibly be leading to worse outcomes.  Echo (transthoracic or transesophageal) is a very accurate modality for assessing volume status, ventricular systolic function, cardiac output, etc. which makes it an excellent diagnostic tool, but it is an expensive technology and is highly dependent on operator experience, so it is not routinely appropriate for monitoring.  A new “goal-directed” approach to volume resuscitation is now present through new technologies that use a dynamic approach.  Arterial pressure wave form systems including the PiCCO, PulseCO, and FloTrac/Vigileo are less invasive and can possibly better assess volume status using the calculated values of stroke volume variation, pulse pressure variation, stroke volume, stroke volume index, cardiac output, and cardiac index.  SVV and PPV are more reliable indicators of volume responsiveness than SVP, PAOP, left ventricular rend diastolic volume index, and global end-diastolic volume index. 

The type of fluid is also important in volume resuscitation, and typical choices include crystalloids, colloids, hypertonic saline, or blood products.  Crystalloids are typically the beginning choice as they are inexpensive, plentiful and easy to administer.  However, they do not linger long in the bloodstream, can predispose a patient to hyperchloremic metabolic acidosis (NS), they do not carry oxygen, and can impede clotting, and are therefore be of limited value in resuscitation of hemorrhaging patients.  Colloids (hextend and albumin) are of value in that they can play a role in controlling cerebral blood flow, can preserve the microcirculation with a minimum volume, they may have anti-inflammatory properties, and remain in the intravascular space longer than crystalloids.  However, they may negatively affect coagulation or cause pulmonary edema at large doses, and have a higher risk of anaphylaxis.  Hypertonic saline is a newer and evolving modality involving small volume resuscitation.  Hypertonic saline acts like a magnet, drawing fluid from tissues into the bloodstream, thereby increasing circulating volume; additionally, it keeps this fluid in the intravascular space much longer than crystalloid.  It may improve microvascular flow, control ICP, and stabilize arterial pressure and cardiac output.  However, meta-analysis of clinical studies shows no significant improvement in survival with the use of hypertonic solutions for resuscitation in hemorrhagic shock at this time.  Finally, the pros and cons of utilizing blood products are well established.  Administration of blood products (including pRBCs, whole blood, FFP, and platelets) in the face of hemorrhage restores oxygen carrying capacity and supports coagulation; however, the “evils” of transfusion are well described, transfusion related acute lung injury is a common complication of FFP administration, and there is little doubt that increased exposure to blood products increases the long term risk of inflammatory complications.

In summary, resuscitation depends on correctly identifying the underlying pathophysiology, expediting surgical control, and supporting organ system perfusion.  Fluid administration is the mainstay of resuscitation but must be approached in a systematic fashion.  No perfect monitor exists to indicate the patient’s degree of shock, but newer modalities are promising.  In actively hemorrhaging patients, there is evidence to sugges3t that attempting to normalize blood pressure will increase mortality, and the timing and rate of fluid administration play a critical role in hemostasis.  Early use of blood products, especially plasma, may help to prevent the onset of coagulopathy.  The tactic of choice for managing patients with sepsis involves early fluid administration, judicious monitoring, and surgical control of the pathology, if necessary.

Microcirculation and Sepsis Treatment, Dr. Perz

Katie Perz, D.O.

Article:

Early Increases in Microcirculatory Perfusion During Protocol-Directed Resuscitation are Associated with Reduced Multi-Organ Failure at 24 hours in Patients with Sepsis

Trzeciak, S., McCoy, J., Dellinger, P., Arnold, R., Rizzuto, M, Abate, N., Shapiro, N., Parrillo, J., Hollenberg, S.,

Summary:

Sepsis is a common and lethal disease.  Development of acute multi-organ failure is one of the primary determinants of sepsis mortality.  Early evidence of multi-organ failure and early changes in organ function, specifically changes over the first 24 hours of severe sepsis presentation, are especially prognostic.  The objective of this article was to investigate whether changes in microcirculatory blood flow during the first 24 hours of sepsis are associated with changes in organ failure.  The study used direct visualization of the sublingual microcirculation with sidestream dark field (SDF) videomicroscopy to detect direct and indirect assessments of tissue perfusion.  Using this initial SDF, early goal directed therapy was initiated, and results were measured using a sequential organ failure assessment score. This score took respiration (PaO2/FiO2), coagulation (platelet levels), liver tests (bilirubin levels), cardiovascular status (hypotension or pressor use), and renal status (Creatinine levels) to evaluate the effectiveness of early goal directed therapy following microcirculation visualization with SDF videomicroscopy.

The article concluded that early increases in microcirculatory blood flow during protocol-directed resuscitation were associated with reduced organ failure at 24 hours in patients with sepsis.  The data supported the hypothesis that goal directed fluid therapy targeting the microcirculation distinct from the macrocirculation could potentially improve organ failure in sepsis.

Hemodynamic Parameters to Guide Fluid Therapy, Dr. Perz

Katie Perz, DO

Hemodynamic Parameters to Guide Fluid Therapy

Paul E Marik, Xavier Monney, Jean-Louis Teboul

Journal Ann Intensive Care, 2011

Introduction: The cornerstone of treating patients with shock remains as it has for decades: IV fluids.  Surprisingly, dosing IV fluid during resuscitation of shock remains largely empirical.  Multiple studies have demonstrated that only approximately 50% of hemodynamically unstable patients in the ICU and OR respond to a fluid challenge.  Cardiac filling pressures, including CVP and PAOP have been traditionally used to guide fluid management, but studies during the past 30 years have demonstrated that cardiac filling pressures are unable to predict fluid responsiveness.  During the past decade, a number of dynamic test of volume responsiveness have been reported.  This article outlines a recommendation for assessing hemodynamic management with consideration of useful parameters for volume status and ventilatory status of the patient (mechanically vs. spontaneous vs. combination).

Recommendations for accurately assessing volume status:

1.     Pulse Pressure Variation (PPV):

a.     Derived from analysis of arterial waveform

b.     Some authors predict that PPV was a reliable predictor of fluid responsiveness only when tidal volumes are >8mL/kg

2.     Stroke Volume Variation (SVV):

a.     Derived from pulse contour analysis

3.     Pulse Oximeter Plethysmographic Waveform Amplitude Variation

a.     Dynamic changes of this waveform with positive pressure ventilation have shown a significant correlation and good agreement with the PPV and have accurately predicted fluid responsiveness in the OR in ICU

4.     Doppler Echocardiography

a.     Respiratory changes in aortic blood velocity as measure by TEE can predict fluid responsiveness in mechanically ventilated patients

b.     Changes in vena-caval diameter can be measured to predict fluid responsiveness

5.     End Expiratory Occlusion Test

a.     Interrupting mechanical ventilation during an end-expiratory occlusion can increase cardiac preload sufficiently for such a test being used to predict fluid responsiveness

6.     Passive Leg Raising

a.     Can be used in patients who are mechanically ventilated or those who have a spontaneous component to their mechanical ventilation

b.     The change in aortic blood flow, measured by esophageal Doppler, during a 45 degree  leg elevation was shown to predict the changes in aortic blood flow produced by a 500mL fluid challenge even in patients with arrhythmias and/or spontaneous ventilator triggering (a situation when PPV loses its predictive ability)

c.     Can be assessed with use of Flo-trac Vigileo, PiCCO, or NICOM devices

                                               i.     Less invasive than PA catheterization but not ideally suited to resuscitate in the ER or ward.

Conclusion: All these methods have a useful place in the continuum of the resuscitation process.  This article recommends that CVP no longer be used to guide fluid management in the OR, ICU or ER.