Critical Illness, Dynamic Arterial Elastance, Fluid Over-load, Septic Shock
Conditions
Keywords
critical illness, dynamic arterial elastance, stroke volume change prediction, fluid overload, ischemic complication, septic shock
Brief summary
To investigate the benefit of using the AFM and Eadyn-guided fluid and vasopressor therapy in septic shock resuscitation for mechanically ventilated patients compared with the standard of care. The investigators hypothesize that using the AFM and Eadyn-guided fluid/vasopressor titration in septic shock patients who underwent mechanical ventilation might reduce the time to shock reversal.
Detailed description
Hypotension in the context of an intensive care unit has been associated with a higher risk of death and multiorgan dysfunction. Vascular leakage and systemic vasodilatation are brought on by systemic inflammation from infections. These are the hallmarks of septic shock in which 90% of cases of shock are mostly distributive and hypovolemic. Early vasopressors and fluid therapy are increasingly used at the start of vasodilatory shock resuscitation since this method improves the rate of shock control within 6 hours in septic shock resuscitation. Norepinephrine is the first-line vasopressor for vasodilatory shock. However, resuscitation with an accurate amount of fluid and vasopressor is challenging in clinical practice. Fluid overload and overuse of vasopressors are prevalent and increase mortality. Together with a higher dose of norepinephrine, it may increase the risk of ischemic complications. A new hemodynamic monitoring device (Hemosphere(R) - Edward Lifescience, California, USA) provides two novel parameters for hemodynamic monitoring: the new device with artificial intelligence developed by a retrospective cohort (used for training) and a prospective (local hospital cohort used for external validation). The feature of Hemosphere(R), including dynamic arterial elastance (Eadyn) and stroke volume change prediction (∆SVpredict) as the assist fluid management (AFM) based on arterial pressure waveform analysis by the monitoring software, was detected in arterial line waveform without any complication of a safety issue. The ratio of pulse pressure to stroke volume (PP/SV) is defined by dynamic arterial elastance (Eadyn), the reciprocal of compliance within the range of 0.8 to 1.0 is the optimization of arterial load that can predict arterial pressure response to fluid administration and vasopressor weaning. The prediction of the stroke volume changes following the upcoming fluid therapy (∆SVpredict) uses stroke volume variation parameters and closed-loop feedback data, which should be less than 10% to indicate optimal fluid administration. Consequently, this technique offers a useful means of evaluating arterial tone related to preload responsiveness parameters predicting the hemodynamic response to increases in cardiac preload. However, several studies show the benefit of this tool in perioperative patients, and the evidence on the benefit of using this monitoring to guide septic shock resuscitation is limited. In a previous study, Eadyn can predict a decrease in mean arterial pressure linked to a reduction in norepinephrine dosage. This study aimed to investigate the benefit of using AFM and Eadyn-guided fluid and vasopressor therapy in septic shock resuscitation compared with the standard of care
Interventions
DEVICEThe AFM and Eadyn - guided resuscitation group
A fluid challenge using a stroke volume change prediction (∆SVpredict) and Eadyn guide. If the ∆SVpredict is more than 10%, isotonic crystalloid of 500 ml will be administered in 30 minutes, and the machine's response will be awaited. If ∆SVpredict is still more than 10%, continuous fluid loading was reapplied until SVV was less than 10% (fluid therapy will be stopped if ∆SVpredict is less than 10%) and dynamic arterial elastance (EAdyn) reaches the goal of 0.8-1.0 along with a vasopressor will be administered and titrated every 10 minutes until the target MAP \> 65 mmHg is reached. After MAP of 65 achieved, tissue perfusion including urine output, capillary refill time, and serum lactate will be assessed
OTHERThe standard care for septic shock
The standard of care group will be treated according to according to septic shock guidelines 2021; In brief A vasopressor with optimal ideal fluid (at least 30 ml/kg) will be given to achieve the hemodynamic target (MAP ≥ 65 mm Hg) by fluid challenge technique guided by MAP and central venous pressure (CVP) changes after fluid challenge. Fluid-responsive tests can be used as a subsidiary, depending on the attending physician. Early Norepinephrine (NE) infusion can be used with a standard dose of 0.05 mcg/k/min and titrated at the rate of 0.01-0.02 mcg/kg/min every 10 min until 0.25 mcg/kg/min was achieved; then, the second line vasopressor will be added and adjusted to the target of vasopressor. Hydrocortisone can be given according to septic shock guidelines. After MAP of 65 achieved, tissue perfusion including urine output, capillary refill time, and serum lactate will be assessed
Sponsors
Mahidol University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
A fluid challenge using a stroke volume change prediction (∆SVpredict) and Eadyn guide. If the ∆SVpredict is more than 10%, isotonic crystalloid of 500 ml will be administered in 30 minutes, and wait for the response of the machine for 5 minutes after loading. If ∆SVpredict is still more than 10%, continuous fluid loading was reapplied until SVV was less than 10% (fluid therapy will be stopped if ∆SVpredict is less than 10%) and dynamic arterial elastance (EAdyn) reaches the goal of 0.8-1.0\[5\] along with a vasopressor will be administered and titrated every 10 minutes until the target mABP \> 65 mmHg is reached.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All Thai consecutive patients older than 18 years with a diagnosis of sepsis or septic shock in medical ICU, defined by clinically suspected or confirmed infection and MAP \<65 mmHg according to the criteria of the Surviving Sepsis Campaign 2021(11)with onset of shock in less than 24 hours. * Already receiving or planning for mechanical ventilation * Already receiving or planning for arterial catheter placement for invasive arterial pressure monitoring * All patients will receive an echocardiogram with a cut point of LVEF \> 30% to be included in the study
Exclusion criteria
* Active, immediate, life-threatening cardiac arrhythmia, defined as ventricular tachycardia and ventricular fibrillation * Acute cerebral vascular event, including both acute ischemic stroke or intracranial hemorrhage * Acute coronary syndrome * cardiogenic shock, acute heart failure * Severe asthma exacerbation * Fluid intolerance: hypoxemia (P:F ratio \< 150) * Life-threatening gastrointestinal hemorrhage * Pregnancy * Requirement for immediate surgery within 2 hours of randomization * Advanced-stage cancer with predicted survival of less than 6 months * Oliguric AKI with signs of volume overload Withdrawal or termination criteria * The patient and legal representative request for withdrawal * The attending physician requested a withdrawal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| time to shock reversal | 28 days | the time from diagnosis of septic shock until the achievement of sustained MAP of ≥65 mmHg with evidence of adequate tissue perfusion (continuation of urine flow ≥ 0.5 ml/kg/h or normalized or continuing decrease in serum lactate ≥10% from the previous value) without any vasopressor infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| a time-to-goal achievement for septic shock resuscitation | 28 days | MAP ≥ 65 mmHg with vasopressors and optimized tissue perfusion |
| time to NE titrating | 48 hours | — |
| maximum dose of vasopressors | 48 hours | — |
| volume of fluid therapy during resuscitation | 48 hours | — |
| fluid before randomization | 48 hours | — |
| fluid accumulation at 24 hours | 24 hours | — |
| fluid accumulation at 72 hours | 72 hours | — |
| fluid accumulation at 7 days | 7 days | — |
| 28-day hospital mortality | 28 days | — |
| hospital length of stay | 28 days | — |
| shock reversal at 6 hours | 6 hours | Shock reversal is defined as mean arterial pressure at or more than 65 mmHg with one of the following: -Reduction of serum lactate level of 20% or more -Hourly urine output of 0.5 mL/kg or more |
| rate of new initiation of renal replacement therapy | 28 days | — |
| time to initiation of renal replacement therapy | 28 days | — |
| Vasopressor-free day | 28 days | Number of days that patient is alive after successful discontinuation of vasoactive agents in the first 28 days, with the day of randomization defined as Day 1. Successful discontinuation of vasoactive agents is defined as discontinuation of vasoactive agents without resumption until Day 28 or until hospital discharge, whichever is first. In case of multiple periods of vasoactive agents use, the days from the final discontinuation of vasoactive agents are counted. All 28-day non-survivors are counted as 0, irrespective of their use of vasoactive agents at the time of death, and censored observations after 28 days |
| Ventilator-free day | 28 days | Number of days that patient is alive after successful liberation of mechanical ventilation in the first 28 days, with the day of randomization defined as Day 1. Successful liberation of mechanical ventilation is defined as the discontinuation of mechanical ventilation (either via orotracheal or tracheostomy tube) for 48 hours or more. Non-invasive positive pressure ventilation is not regarded as mechanical ventilation. In case of multiple periods of mechanical ventilation, the days from the final successful liberation of mechanical ventilation within 28 days are counted. All 28-day non-survivors are counted as 0, irrespective of their ventilation status at the time of death, and censored observations after 28 days |
| Renal replacement therapy(RRT)-free day | 28 days | Number of days that patient is alive after successful discontinuation of renal-replacement therapy in the first 28 days, with the day of randomization defined as Day 1. Successful discontinuation of renal-replacement therapy is defined as discontinuation of all modes of renal-replacement therapy without resumption for at least 7 days and until Day 28 or until hospital discharge, whichever is first. Hemoperfusion according to treatment protocol in 'Standard of care and hemoperfusion with HA-330' arm is not counted as renal-replacement therapy. All 28-day non-survivors are counted as 0, irrespective of their use of renal-replacement therapy at the time of death, and censored observations after 28 days |
| Serum lactate at 0 hours, 1 hour, and 6 hours | 6 hours | — |
| ICU length of stay | 28 days | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| adverse event | 28 days | ischemic complication and arrhythmia |
Countries
Thailand
Contacts
Primary ContactRanistha Ratanarat, MD
Backup ContactNuwara Pornawalai, MD
Outcome results
None listed