The Randomized Controlled Trial of Inferior Vena Cava Ultrasound-guided Fluid Management in Septic Shock Resuscitation

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.

• IVC Ultrasound-guided (Procedure): 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 (Drug), also known as Antimicrobials: Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.
• Vasopressor (Drug), also known as Norepinephrine, dopamine, epinephrine: 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.

Primary outcomes

• 30-day Mortality [30 day after randomization]: 30-day mortality related to septic shock

Secondary outcomes

• 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.

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• 30-day Mortality (Primary), Count of participants, Participants: IVC Ultrasound-guided 20; Usual Care 19
• Percentage Change of 6-hour Lactate (Secondary), Median, percentage change: IVC Ultrasound-guided 39.2 (7.4 to 60); Usual Care 35.9 (16.3 to 65.5)
• 6-hour Cumulative Amount of Intravenous Fluid (mL) (Secondary), Median, mL: IVC Ultrasound-guided 1900 (1500 to 2570); Usual Care 2600 (2300 to 3220)
• 72-hour Cumulative Amount of Intravenous Fluid (mL) After Treatment (Secondary), Mean, mL: IVC Ultrasound-guided 7,300 (5040 to 9200); Usual Care 7,702 (5900 to 11275)
• Change in Sequential Organ Failure Assessment (SOFA) Score in 72 Hours After Treatment (Secondary), Median, Score on a scale: IVC Ultrasound-guided 1 (-1 to 3); Usual Care 1 (-1 to 2)

Adverse events

Time frame: 30 days

Serious adverse events by term

Other adverse events by term

Limitations and caveats: This study was conducted with the specific study protocol at a single, tertiary-care hospital. Second, physicians should use cautious clinical judgment or different approaches in different types of patients. The interpersonal variation and sampling position may have affected the consistency of IVC diameter measurement.

• Musikatavorn K, Plitawanon P, Lumlertgul S, Narajeenron K, Rojanasarntikul D, Tarapan T, Saoraya J. Randomized Controlled Trial of Ultrasound-guided Fluid Resuscitation of Sepsis-Induced Hypoperfusion and Septic Shock. West J Emerg Med. 2021 Feb 10;22(2):369-378. doi: 10.5811/westjem.2020.11.48571. PMID 33856325

• Study Protocol and Statistical Analysis Plan (PDF, 2020-10-01)

• Khrongwong Musikatavorn, MD, Principal investigator, Emergency Unit, Faculty of Medicine, Chulalongkorn Hospital