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Septic Shock Management Guided by Ultrasound: SEPTICUS Trial

Not Applicable
Conditions
Septic Shock
Interventions
Procedure: USSM protocol
Procedure: ACCM protocol
Registration Number
NCT04728529
Lead Sponsor
Saptadi Yuliarto
Brief Summary

This clinical study aims to compare the recent septic shock management protocol from American College of Critical Care Medicine (ACCM) to Ultrasound-guided Septic Shock Management (USSM) protocol. USSM protocol laid on Doppler ultrasonography to evaluate stroke volume, cardiac index, and systemic vascular resistance in each step of management to decide the proper fluid resuscitation and vasoactive therapy; differs from ACCM protocol which use clinical finding in its early step. ACCM protocol application elicits risk of improper therapy since clinical sign per se often could not describe the certain cardiac output. This can be prevented earlier by USSM protocol. The outcome compared of the two protocols is: mortality rate, clinical parameter, macrocirculation hemodynamic parameter, laboratory microcirculation parameter, and signs of fluid overload. The investigators hypothesized if the USSM protocol had a better outcome and less fluid overload complication.

Detailed Description

This study is a randomized controlled trial to compare the usage of ACCM protocol and USSM protocol in fluid resuscitation for septic shock pediatric patients. The USSM protocol is the intervention, and the ACCM protocol is the control. This study implemented in septic shock pediatric patients treated in the intensive care unit. Each patient will be randomized into 2 groups, the USSM group or the ACCM group. In the initial step, all patient in each group will receive early acute/emergency therapy: oxygen support, vascular access, and fluid resuscitation. The monitoring of the patient including clinical parameters and laboratory examination for both groups, except Doppler ultrasonography that performed in each step of management of the intervention group. The monitoring is performed every 15 minutes in the first hour of resuscitation. If the patient show good response (fluid responsive shock), the monitoring stops in 1 hour. In contrast, if the patient reveal fluid refractory shock, the vasoactive agent will be administered and monitoring continues until 6 hours. All outcome parameters, except mortality rate, will be recorded at 6 hours. The mortality rates will be recorded at 72 hours and time of intensive care discharge.

Sample size in this study was calculated by clinical trial formula for mortality rate with a significance level of 0.05 and study power of 0.2. From the calculation, the subject needed is 170 patients for each group (total 340 subjects). The basic characteristics of the patient will be analyzed descriptively. All parameter data will be analyzed statistically by Statistical Product and Service Solution (SPSS) 20, preceded by normality test and homogeneity test. The study analysis will be intention-to-treat. The mortality rate was analyzed by Kaplan-Meier survival analysis. Data transformation will be performed if needed in case of outlier data or out-of-range results.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
340
Inclusion Criteria
  • diagnosed as septic shock according to Pediatric Surviving Campaign (2005)
Exclusion Criteria
  • patient with uncorrected congenital heart disease with shunting
  • obtain fluid resuscitation before recruitment process
  • obtain inotropic-vasoactive agent before recruitment process
  • after undergo any heart surgery

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
USSM protocolUSSM protocolpatient in the intervention group receive fluid resuscitation and inotropic-vasoactive agent, if needed, in accordance to USSM protocol of fluid resuscitation.
ACCM protocolACCM protocolpatient in the control group receive fluid resuscitation and inotropic-vasoactive agent, if needed, in accordance to ACCM protocol of fluid resuscitation.
Primary Outcome Measures
NameTimeMethod
Mortality rate72 hours of the initial fluid resuscitation

Time of mortality occurrence since randomization, comparing intervention and control group.

Number of mortality72 hours of the initial fluid resuscitation

Amount of non-survivor subject, comparing intervention and control group.

Secondary Outcome Measures
NameTimeMethod
Mean arterial pressure1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Mean arterial pressure (MAP) is measured by vital sign monitor device and reported in mmHg, and classified into hypotension (below 5th percentiles according to age of PALS criteria), normal (above or equal than 5th percentiles according to age of PALS criteria), and high (above 95th percentiles according to age of PALS criteria).

Stroke volume index1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Stroke volume index (SVI) is measured by USCOM, reported in mL/m2, and classified into low (below 30), normal (30 to 60), and high (above 60).

Cardiac index1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Cardiac index (CI) is measured by USCOM, reported in L/minute/m2, and classified into low (below 3.3), normal (3.3 to 6.0), and high (above 6.0).

Vasoactive-inotropic score (VIS)1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

The Vasoactive-Inotropic Score (VIS), quantifies the amount of cardiovascular support required by subjects and includes dopamine, dobutamine, epinephrine, milrinone, vasopressin, and norepinephrine.

Capillary refill time1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Capillary refill time is measured by pressing forehead and sternal skin; time needed for the pink color to return will be measured and reported in second, then classified based on WHO criteria, into prolonged (above 3 seconds) or normal (below or equal than 3 seconds).

Base deficit1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Base deficit is measured by blood gas analysis examination, reported in mmol/L, and classified into low (below -3), normal (-3 to 3), and high (above 3).

Blood lactate level1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Blood lactate level is measured from arterial blood, reported in mmol/L, and classified into normal (below or equal to 2.0) or high (above 2.0).

Lung ultrasound score1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Lung Ultrasound Score is examined with ultrasound using linear transducer (7.5 to 11 Mhz) to measure pulmonary parenchyma aeration on 12 scan areas (6 areas in each hemithorax), by a doctor who is ultrasound-certified lung. Each hemithorax is divided by 3 vertical lines (parasternal, anterior axillary, and posterior axillary) so that it becomes 3 areas (anterior, lateral, and posterior); and 1 horizontal line dividing the hemithorax into 2 equal parts. In each area a score is recorded. The final result is a total score of 12 areas. The scores are stated as follows:

i. 0 = no (or very few) B-lines ii. 1 = B-lines look many but separate (separated B-lines) iii. 2 = many B-lines and converge (coalescent B-lines) iv. 3 = lung consolidation

Heart rate1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Heart rate is measured by vital sign monitor device, reported in beat/minute, and classified into bradycardia (below normal rate according to age of PALS criteria), normal, and tachycardia (above normal rate according to age of PALS criteria).

Systolic blood pressure1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Systolic blood pressure is measured by vital sign monitor device and reported in mmHg, and classified into hypotension (below 5th percentiles according to age of PALS criteria), normal (above or equal than 5th percentiles according to age of PALS criteria), and high (above 95th percentiles according to age of PALS criteria).

Liver span increase1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

The increase of liver span is clinically measured from mid-costal right arch to the edge of liver, and reported in centimeters.

Peripheral pulse strength1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Peripheral pulse strength is measured by comparing peripheral radial pulse and central (carotid or femoral) pulse, reported qualitatively as weak or normal/strong

Systemic vascular resistance index1 hour in fluid-responsive subject or 6 hour in fluid-refractory subject after fluid resuscitation initiated

Systemic vascular resistance index (SVRI) is measured by USCOM, reported in d.s/cm5/m2, and classified into low (below 800), normal (800 to 1600), and high (above 1600)

Trial Locations

Locations (1)

RSUD dr. Saiful Anwar

🇮🇩

Malang, Jawa Timur, Indonesia

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