BACKGROUND:

The first line of treatment in patients with acute circulatory failure is volume expansion. Only half the patients with circulatory failure positively respond to fluid administration. Excessive fluid loading is associated with increased complications, mortality and length of intensive care unit stay. An accurate prediction of fluid responsiveness may prevent unnecessary fluid loading and detect patients who benefit from volume expansion. Predicting which patients will respond to fluid administration by increasing cardiac output is a challenge in critically ill patients.

Traditionally used static hemodynamic monitoring indicators, like central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP) etc., are of limited value in predicting fluid responsiveness in critically ill patients. Various dynamic indices like systolic pressure variation (SPV) stroke volume variation (SVV) and pulse pressure variation (PPV) based on cardiopulmonary interactions in ventilated patients have been shown to accurately predict fluid responsiveness. Of these parameters, PPV is supported to be having the highest level of evidence. However, PPV has certain limitations. It cannot be used, or is not reliable in certain conditions like patients with spontaneous breathing activity, cardiac arrhythmias, low tidal volume, high frequency ventilation, high intra abdominal pressure, open chest.

Low TV ventilation (≤ 6 ml/kg IBW) is commonly used in patients with sepsis, acute lung injury/acute respiratory distress syndrome (ALI/ARDS). During low tidal volume ventilation, PPV may be unreliable because a low TV might be insufficient to produce a significant change in the intra thoracic pressure. In these patients PPV may indicate a non-responsive status even in responders. Another important factor may be that respiratory rate is often high when ventilating with low tidal volume. PPV has been observed to be negligible in fluid responders when the ratio of heart rate to respiratory rate was decreased below 3.6. Muller and colleagues recently confirmed this finding. 

Previous clinical and experimental studies have conflicting results regarding the accuracy of PPV measured with a TV below 8 ml/ kg. De Backer et al evaluated the influence of tidal volume on ability of PPV to predict fluid responsiveness and showed PPV is reliable only if the tidal volume is >8ml/kg since tidal volume, but not airway pressure, was the main determinant of right ventricular afterload and right ventricular stroke work, two main components of PPV. Lansdorp et al showed that PPV and other such dynamic indices are only reliable under strict conditions and low tidal volume can substantially reduce their predictive value.They proposed correcting PPV for the applied tidal volume to improve its predictive value at low tidal volume Muller et al showed that in patients ventilated with low tidal volume, PPV values <13% does not rule out fluid responsiveness, especially when the airway driving pressure is <or =20 cmH(2)O. Lakhal et al also showed the poor performance of PPV in early ARDS patients ventilated with low tidal volume in predicting fluid responsiveness.

Huang et al showed that PPV accurately predicts the response of cardiac output to volume expansion and remains a reliable predicator of fluid responsiveness for early ARDS patients ventilated with low tidal volume and high PEEP and Freitas et al showed the accuracy of PPV was adequate in patients with septic when they were ventilated with a TV of 6 ml kg and even devised cut-off value of 6.5% to discriminate between the responders and non-responders .

To overcome limitations with PPV while ventilating patients with low tidal volume, alternative tests have been proposed to assess fluid responsiveness such as End Expiratory Occlusion Test (EEOT), Passive leg raising test (PLRT) and mini fluid challenge. Of these, the recently proposed EEOT is a relatively simple bedside test that can reliably predict fluid responsiveness. Studies that tested EEOT used tidal volumes between 6.3 - 8.8 ml/kg predicted body weight (PBW). However, during protective lung ventilation a tidal volume of ≤ 6 ml/kg IBW is recommended. Whether EEOT would provide adequate volume to challenge the system at such low tidal volumes, has not been tested.

We propose using PPV itself, to assess fluid responsiveness, in patients ventilated using lower tidal volume, by measuring it after transiently increasing the TV from 6 to 8ml/kg IBW and back to 6ml. We hypothesize that transiently increasing TV to 8 ml/kg and measuring PPV may help unmask fluid responders.Though the PPV may increase in both responders and non responders, we hypothesise that the change in PPV (     PPV) may not be the same in both.The    PPV may be indicative of fluid responsiveness.

A tidal volume of 6 ml/kg PBW is recommended in patients with ARDS. We think transiently increasing tidal volume for one minute to 8 ml/kg PBW should be safe, as it is similar to giving a recruitment maneuver (RM). RMs are often used in ventilated patients, a strategy to increase the transpulmonary pressure transiently with the goal to reopen those alveolar units that are not aerated or poorly aerated but reopenable and are recommended in patients with hypoxemia due to ARDS.

A fluid challenge of 7 ml/kg actual body weight of saline will be given over 10   minutes at the end of the study.  Our study will include only those patients in whom a clinician has planned to give a fluid challenge. The international Guidelines for Management of Severe Sepsis and Septic Shock recommends that a fluid challenge technique should be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic or static variables.

Patients will be divided into two groups “Responders” and “Non-Responders” based on an increase in Cardiac index >15% after giving the fluid bolus. This will help us determine whether measuring PPV while transiently increasing tidal volume will help us unmask true responders.  This test has the potential to be a simple bedside test, not requiring any change in posture or the use of a continuous cardiac output monitor to assess fluid responsiveness.