Monitoring Resuscitation in Severe Sepsis and Septic Shock

Study Overview
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Brief Summary
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Our hypothesis is that hemodynamic fluid resuscitation guided by dynamic parameters will improve outcome in patients with severe sepsis and septic shock, by limiting the deleterious effects of fluid overload.

Detailed Description
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To evaluate the efficacy of dynamic parameters versus static measures to guide fluid resuscitation we pretend to detect a 10% relative reduction in mortality. In addition, we pretend to observe an improvement on the length of resuscitation time, mechanical ventilation and vasopressor support-free days, ICU and hospital length of stay, organ failure and renal function.

Official Title
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Monitoring Resuscitation in Severe Sepsis and Septic Shock

Conditions
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Hemodynamics

Intervention / Treatment
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* Behavioral: Dynamic-parameters-guided fluid management
* Behavioral: Standard-guided-fluid management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Clinical evidence of sepsis (microbiology confirmation, radiological or direct view - pus in biological fluid or surgical direct view-). ≥ 2 SIRS criteria: Temperature < 36.0°C or > 38.0°C Heart rate > 90 bpm Respiratory rate > 20 rpm or PaCO2 < 32 mmHg or need of mechanical ventilation. Leukocytes > 12.0 x109/L or < 4.0 x109/L Hemodynamic insufficiency defined as (at least one of the following): Sustained systemic hypotension (systolic arterial pressure ≤ 90 mmHg or MAP < 65 mmHg) or a decrease in MAP of > 30 mm Hg in a hypertensive patient. Need of vasopressors. Tachycardia (HR > 110 bpm) or bradycardia (HR < 55 bpm) Acute onset of oliguria, defined as a decreased urine output < 0.5 ml/kg/hr for ≥ 2 hours Serum lactate > 2 mmol/l Peripheral cyanosis, mottled skin, prolonged capillary refill Mechanical ventilation without any kind of inspiratory effort and Vt 7-10 mL/Kg, Pplateau < 30 mmH2O. Those patients with ARDS under mechanical ventilation will need to tolerate a tidal volume of at least 7 mL/Kg during 30 seconds while the plateau pressure remains < 30 mmH2O. Prior hemodynamic monitoring by arterial catheter. Central venous catheter. Exclusion Criteria: Acute myocardial infarction < 7 days. Pregnancy Prior request of limited code status or expected life length lower than 3 months. Shock > 12h Cardiac arrhythmia Aortic valvular disease Inability to properly measure arterial pressure wave forms

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dynamic guide resuscitation<br>This arm follows a resuscitation protocol based on dynamic-parameters-guided fluid management. | Behavioral: Dynamic-parameters-guided fluid management<br>* ● In preload-responsive patients defined by the following dynamic parameters: Patients fully adapted to mechanical ventilation* and with sinus rhythm. PPV >12%. PPV: Pulse pressure variation PPV = (PPmax-PPmin)/ [(PPmax+PPmin)/2] x100 (during 5 respiratory cycles) SVV > 12% (15). SVV: Stroke volume variation A tidal volume (Vt) ≥ 7-10cc/kg in mechanically ventilated (in a controlled mode - control volume or control pressure) and well-adapted patients without any inspiratory effort should be guaranteed. Fluid loading must be performed with crystalloids (1omL/Kg) or colloids (5ml/Kg) every 30 minutes until PPV-SVV < 12%, while hypoperfusion signs are present. Continue resuscitation following Surviving Sepsis Campaign rules excluding more fluid administration (as described in the standard intervention once CVP>12). ● Non-preload responsive patients (defined as PPV or SVV < 12%) will resume the same protocol as responders when fluid response parameters are negative.<br>|
| Active Comparator: Standard resuscitation<br>This arm follows a common resuscitation protocol based on Surviving Sepsis Campaign recommendations. | Behavioral: Standard-guided-fluid management<br>* Fluid loading in patients with hypotension or elevated lactates until normalization of MAP (> 65mmHg) or CVP > 12mmHg. If CVP reaches > 12 mmHg and MAP remains < 65mmHg, norepinephrine should be started to reach MAP > 65mmHg. Once MAP is restored, if hypoperfusion signs persist (elevated lactate or urine output < 0.5mL/Kg/h), ScvO2/SvO2 must be measured. In order to reach a ScvO2 ≥70% or SVO2 ≥65%, consider giving blood transfusion if hemoglobin level (Hb) ≤ 7g/dL, and also consider dobutamine (initial dose 2,5 µg/kg/min, increased by 2,5 µg/kg/min every 30 min up to a maximum dose of 20 µg/kg/min, presence of arrhythmia, or FC>110bpm). At that point, if hypoperfusion signs remain present, consider restart protocol from the beginning.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at 28 days |  | 28 days after hospital admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of resuscitation | Vasopressor use and fluid load between 0h to 6h Vasopressor use and fluid load between 7h to 72h | 72 hours after protocol inclusion | 
| Ventilator-free days | From 1 to 28 days over 28 days in a month. | 28 days after admission | 
| Vasopressor-free days | From 1 to 28 days over 28 days in a month. | 28 days after admission | 
| Organ failure-free days | Cardiovascular, CNS, renal, hepatic, coagulation abnormalities. From 1 to 28 days over 28 days in a month. | 28 days after admission | 
| ICU length of stay |  | At ICU discharge (expected average 30 days after admission) | 
| Hospital length of stay |  | At hospital discharge (expected average 45 days after hospital admission) | 
| Renal function evolution | Creatinin clearance will be calculated every day for the first 3 days (Cockroft-Gault formula). | 3 days after study enrollment | 
| Mortality at 3 months |  | 3 months after admission |