Septic Shock
Conditions
Keywords
Septic Shock, Inferior vene cava diameter, Resuscitation, Mortality
Brief summary
The primary aim of this study is to evaluate the 30-day mortality outcome of the septic shock patients who are treated with ultrasound-assisted fluid management using change of the inferior vene cava (IVC) diameter during respiratory phases in the first 6 hours compared with those treated with usual-care strategy.
Detailed description
Septic shock (SS) is globally prevalent in with high mortality rate.The current focuses on initial treatment of this condition emphasize on the early recognition, prompt administration of antibiotic, and restoration of hemodynamic with aggressive fluid resuscitation and vasopressor. Regarding the initial fluid therapy, administration of empirical crystalloid at the dose of 30 ml/kg is recommended in the guideline. The ultrasound-assisted management of shock patients has been introduced in the past decade and now is widely used. By using the measurement of inferior vena cava (IVC) diameter change during respiratory phases, physicians can predict the fluid responsiveness in the shock patients and tailor the fluid therapy during the resuscitation.Unfortunately, clinical outcome related to the use of this concept in SS resuscitation has not been well studied. Inadequate resuscitation with fluid therapy is related with higher mortality; however, fluid bolus or positive fluid balance that may result from too aggressive fluid administration is also associated with increased mortality in SS patients. The primary aim of this study was to evaluate the 30-day mortality outcome of the SS patients who were treated with ultrasound-assisted fluid management using change of the IVC during respiratory phases in the first 6 hours compared with those who were treated with usual-care strategy. The secondary outcomes were to compare the rate of the need for mechanical ventilation (MV) and renal replacement therapy (RRT) as well as the 6-hours lactate clearance and the change in Sequential Organ Failure (SOFA) score in 72 hours.
Interventions
PROCEDUREIVC Ultrasound-guided
IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
DRUGAntibiotics
Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
DRUGVasopressor
The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.
Sponsors
Chulalongkorn University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient who attended the emergency department with septic shock (defined by those who require a vasopressor to maintain a mean arterial pressure (MAP) of 65 mm Hg or greater and whose serum lactate level greater than 2 mmol/L in the absence of hypovolemia.)
Exclusion criteria
* 1\) Congestive pulmonary edema or known to have poor systolic cardiac function (left ventricular ejection fraction ≤ 40%). * 2\) Known to have right heart pathologies. * 3\) Having or suspected to have marked ascites, significant bowel dilatation or the conditions that can cause abdominal hypertension. * 4\) Body mass index ≥ 30 kg/square meter. * 5\) Having concomitant attack of severe airway disease (eg. Asthma, COPD) that may have confounded the IVC interpretation due to the positive intrathoracic pressure. * 6\) IVC can not be identified or its diameter cannot be measured correctly. * 7\) Having end-stage renal diseases with or without dialysis. * 8\) Having non-infectious diseases as final diagnoses. * 9\) Pregnant women. * 10\) Have been referred or treated from other healthcare facility. * 11\) Having active hemorrhages. * 12\) Duplicated cases. * 13\) who had do-not-resuscitate living will. * 14\) Declined to consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 30-day Mortality | 30 day after randomization | 30-day mortality related to septic shock |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change of 6-hour Lactate | 6 hours after treatment | The percentage change in blood lactate at 6 hour after initiation of treatment, calculated by \[(Initial blood lactate level at presentation - blood lactate level at 6 hours after treatment)/Initial blood lactate level at presentation\] x 100%. The higher positive value means the more relative reduction of blood lactate after treatment from that of initial presentation and indicates a better clinical outcome. |
| 6-hour Cumulative Amount of Intravenous Fluid (mL) | 6 hours after treatment | Cumulative amount of intravenous fluid (mL) during the first 6 hours after treatment. |
| 72-hour Cumulative Amount of Intravenous Fluid (mL) After Treatment | 72 hours after treatment | Cumulative amount of intravenous fluid (mL) during the first 72 hours after treatment. |
| Change in Sequential Organ Failure Assessment (SOFA) Score in 72 Hours After Treatment | 72 hours after treatment | The change in Sequential Organ Failure Assessment (SOFA) score between the score at initial presentation and 72 hours after treatment, determined by SOFA score at presentation minus the SOFA score at 72 hours after treatment. The possible minimum and maximum value of the change in SOFA score are -24 and +24, respectively. The higher value means the more relative reduction in SOFA score at 72 hours and indicates a better clinical outcome. |
Countries
Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IVC Ultrasound-guided The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI \> 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI \> 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI \< 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
IVC Ultrasound-guided: IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.
Antibiotics: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
Vasopressor: The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy. | 101 |
| Usual Care Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation. | 101 |
| Total | 202 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | IVC Ultrasound-guided | Usual Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 54 Participants | 52 Participants | 106 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants | 49 Participants | 96 Participants |
| Age, Continuous | 65.3 years STANDARD_DEVIATION 20.1 | 63.7 years STANDARD_DEVIATION 16.8 | 64.5 years STANDARD_DEVIATION 18.5 |
| Patients with infections | 101 Participants | 101 Participants | 202 Participants |
| Race/Ethnicity, Customized Asian | 101 Participants | 101 Participants | 202 Participants |
| Region of Enrollment Thailand | 101 Participants | 101 Participants | 202 Participants |
| Sex: Female, Male Female | 48 Participants | 38 Participants | 86 Participants |
| Sex: Female, Male Male | 53 Participants | 63 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 101 | 19 / 101 |
| other Total, other adverse events | 4 / 101 | 2 / 101 |
| serious Total, serious adverse events | 31 / 101 | 35 / 101 |
Outcome results
Primary
30-day Mortality
30-day mortality related to septic shock
Time frame: 30 day after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IVC Ultrasound-guided | 30-day Mortality | 20 Participants |
| Usual Care | 30-day Mortality | 19 Participants |
Secondary
6-hour Cumulative Amount of Intravenous Fluid (mL)
Cumulative amount of intravenous fluid (mL) during the first 6 hours after treatment.
Time frame: 6 hours after treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVC Ultrasound-guided | 6-hour Cumulative Amount of Intravenous Fluid (mL) | 1900 mL |
| Usual Care | 6-hour Cumulative Amount of Intravenous Fluid (mL) | 2600 mL |
Secondary
72-hour Cumulative Amount of Intravenous Fluid (mL) After Treatment
Cumulative amount of intravenous fluid (mL) during the first 72 hours after treatment.
Time frame: 72 hours after treatment
Population: Data of 72-hour cumulative amount of intravenous fluid was available among 83 patients (missing data in 18 patients; 6 discharge within 72 hours, 5 transfer out, 4 missing records and 3 death within 72 hours) in the Usual care group and 79 patients (missing data in 22 patients, 10 discharge within 72 hours, 4 transfer out, 3 missing records, 5 death within 72 hours) in the IVC Ultrasound-guided group .
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IVC Ultrasound-guided | 72-hour Cumulative Amount of Intravenous Fluid (mL) After Treatment | 7,300 mL |
| Usual Care | 72-hour Cumulative Amount of Intravenous Fluid (mL) After Treatment | 7,702 mL |
Secondary
Change in Sequential Organ Failure Assessment (SOFA) Score in 72 Hours After Treatment
The change in Sequential Organ Failure Assessment (SOFA) score between the score at initial presentation and 72 hours after treatment, determined by SOFA score at presentation minus the SOFA score at 72 hours after treatment. The possible minimum and maximum value of the change in SOFA score are -24 and +24, respectively. The higher value means the more relative reduction in SOFA score at 72 hours and indicates a better clinical outcome.
Time frame: 72 hours after treatment
Population: Data of 72-hour cumulative amount of intravenous fluid was available among 86 patients (missing data in 15 patients; 6 discharge within 72 hours, 5 transfer out, 1 lack of sufficient information and 3 death within 72 hours) in the Usual care group and 78 patients (missing data in 23 patients, 10 discharge within 72 hours, 4 transfer out, 4 lack of sufficient information, 5 death within 72 hours ) in the IVC Ultrasound-guided group .
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVC Ultrasound-guided | Change in Sequential Organ Failure Assessment (SOFA) Score in 72 Hours After Treatment | 1 Score on a scale |
| Usual Care | Change in Sequential Organ Failure Assessment (SOFA) Score in 72 Hours After Treatment | 1 Score on a scale |
Secondary
Percentage Change of 6-hour Lactate
The percentage change in blood lactate at 6 hour after initiation of treatment, calculated by \[(Initial blood lactate level at presentation - blood lactate level at 6 hours after treatment)/Initial blood lactate level at presentation\] x 100%. The higher positive value means the more relative reduction of blood lactate after treatment from that of initial presentation and indicates a better clinical outcome.
Time frame: 6 hours after treatment
Population: Data of 6-hour lactate was obtained among 100 patients (missing data in one patient) in the Usual care group and 100 patients (missing data in one patient) in the IVC Ultrasound-guided group .
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVC Ultrasound-guided | Percentage Change of 6-hour Lactate | 39.2 percentage change |
| Usual Care | Percentage Change of 6-hour Lactate | 35.9 percentage change |