Critical Illness, Shock; Septic
Conditions
Keywords
septic shock, tissue perfusion, macrocirculatory, mean arterial pressure, vasopressor use, days alive free of organ support
Brief summary
Background: The recommended monitoring and target levels in septic shock (SSC Guidelines 2012) including mean arterial pressure (MAP) target are not based on robust clinical data. Objective: To test, if in patients with septic shock, tissue perfusion guided (TPG) treatment strategy leads to a faster resolution of hypoperfusion than the macrocirculatory target guided standard care. Design: A prospective phase II two-parallel-group open-label randomized controlled trial Interventions: 1. Intervention group- Targeted tissue perfusion guided (TTP) - care. 2. Control group - Macrocirculatory - guided (MCG) care. Randomization: 1:1 stratified according to the site and presence or absence of known hypertension. Trial size: 200 randomised patients in 4 ICUs.
Detailed description
Study hypothesis: Targeting at clinical tissue perfusion (in the TTP arm) will decrease the use and untoward effects of vasopressors, and result in more days alive in 30-days without vasopressor or inotropic support and without lactatemia, in comparison with standard clinical care with preference of macrocirculatory targets (MCG arm). Intervention group - Targeted tissue perfusion (TTP) care: Primary targets /registration period 1. capillary refill time (CRT) / \<3 sec/ every hour 2. skin mottling / absent / every hour 3. arterial lactate / \<2.0 mmol/l/ per 2hr 4. peripheral temperature/ warm /every hour 5. urine output/ ≥0.5 mL/kg per hour/ every hour 6. mean arterial pressure (MAP) 50-65 mmHg (minimum as a safety limit)/ continuous * if previous hypertension 65- 70 mmHg * if oliguria 2-hour trial 75-80 mmHg (If diuresis better, continue 2hr and re-evaluate) Secondary target 7. Continuous mixed venous saturation (SvO2) \>65%, if available Control group - Macrocirculatory targets guided (MCG) standard care Primary targets 1. Mean arterial pressure (MAP) 65-75 mmHg /continuous \*\* if previous hypertension 75-80 mmHg \*\*\* if oliguria \< 0.3 ml/kg, 2-hour trial 85-90 mmHg (If diuresis better, continue 2hr and re-evaluate) 2. Central venous pressure (CVP)/hourly, Adequate fluid therapy is indicated to restore clinical hypovolemia up to the recommended CVP-level of 8-12 mmHg, if needed 3. Urine output ≥ 0.5 mL/kg/h/ hourly Secondary target 4. Continuous SvO2 \>65%, if available
Interventions
OTHERHemodynamical treatment TTP
Based on capillary refilling time, peripheral temperature, mottling, diuresis, MAP safety limit monitoring
OTHERHemodynamical treatment MCG
Based on MAP, CVP, urine output monitoring
Sponsors
Insel Gruppe AG, University Hospital Bern
Helsinki University Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Septic shock defined as 1. Septic infection AND 2. systemic mean blood pressure \> 65 mmHg requiring any dose of vasopressors (norepinephrine, vasopressin) despite adequate fluid resuscitation (minimum of 20 ml/kg crystalloids) AND 3. Elevated lactate ≥ 3.0 mmol/L with suspected hypoperfusion
Exclusion criteria
* aged less than 18 or over 80 years * any other probable condition than sepsis affecting or expected to affect the central nervous system including post cardiac arrest * present or suspected myocardial ischemia * acute pulmonary embolism * terminal illness and not considered for full intensive care support * use of extra-corporeal membrane oxygenation (ECMO) * known liver disease - Child-Pugh -Class B or C * confirmed chronic kidney disease known on admission * known to be pregnant or lactating * more than 4 hours from fulfilled inclusion criteria to randomization * another probable cause of hyperlactatemia * patients transferred from another ICU * patients with active haematological malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Days alive in 30 days- without vasopressors/ inotropes or hyperlactatemia | 30 days | • Days alive in 30 days with normal arterial blood lactate ( first confirmed value of \< 2 mmol/L) AND without any inotropic or vasopressor agent |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days alive with normal arterial blood lactate in 30 days | 30 days | — |
| Days alive without any inotropic or vasopressor agent in 30 days | 30 days | — |
| Days alive without renal replacement therapy (RRT) in 30 days | 30 days | — |
| Days alive without mechanical ventilation in 30 days | 30 days | — |
| Time to normalization of arterial blood lactate | 30 days | — |
| New acute kidney injury (AKI) (Kdigo stages I-III) | 30 days | — |
| Days alive outside hospital in 90 days | 90 days | — |
| Total amount of norepinephrine given up to day 5 | 5 days | — |
| Number/ total number of the following adverse reactions | 30 days | ventricular tachycardia/ fibrillation , atrial fibrillation , myocardial infarction , skin necrosis , stroke , secondary bowel ischemia, limb ischemia, numbers of serious adverse events |
| Days alive without any organ support (mechanical ventilation, renal-replacement therapy, vasopressor/ inotropic agents) in 30 days | 30 days | — |
Countries
Finland, Switzerland
Outcome results
None listed