Septic Shock
Conditions
Keywords
Sepsis, Shock, Septic Shock, Fluid Therapy, Resuscitation, Pediatrics, Emergency Medicine, Critical Care
Brief summary
The purpose of the SQUEEZE Trial is to determine which fluid resuscitation strategy results in the best outcomes for children treated for suspected or confirmed septic shock. In this study, eligible children will be randomized to either the 'Usual Care Arm' or the 'Fluid Sparing Arm'. Children will receive treatment according to current ACCM Septic Shock Resuscitation Guidelines, with the assigned resuscitation strategy used to guide administration of further fluid boluses as well as the timing of initiation and escalation of vasoactive medications to achieve ACCM recommended hemodynamic targets.
Detailed description
Please see published pilot trial protocol for more information about the SQUEEZE Trial and rationale for this study.
Interventions
Tier 1: Initiate IV/IO vasoactive medication infusion support immediately. Further IV/IO isotonic fluid bolus therapy \[crystalloid (0.9% Normal Saline or Ringers Lactate) or colloid (5% Albumin)\] should be avoided; small volume isotonic fluid boluses \[5-10 mL/kg (250-500 mL for participants ≥ 50 kg)\] may be provided if required due to A. Clinically unacceptable delay in ability to initiate vasoactive medication infusion(s) and/or 2. Documented intravascular hypovolemia. Tier 2: Vasoactive medication(s) should be preferentially titrated/escalated to achieve recommended ACCM hemodynamic goals. Further IV/IO isotonic fluid bolus therapy \[crystalloid (0.9% Normal Saline or Ringers Lactate) or colloid (5% Albumin)\] should be avoided; small volume isotonic fluid boluses \[5-10 mL/kg (250-500 mL for participants ≥ 50 kg)\] may be provided if required due to A. Documented intravascular hypovolemia. Intervention end: Patient is free from vasoactive medication support and shock is reversed.
Sponsors
Canadian Critical Care Trials Group
Pediatric Emergency Research Canada
Canadian Institutes of Health Research (CIHR)
Canadian Blood Services
Hamilton Health Sciences Corporation
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
29 Days to 17 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria for 1 and 3 must be answered YES to be eligible for study. * Age 29 days to less than 18 years of age * Patient has Persistent Signs of Shock including one or more of the following: * Vasoactive Medication Dependence * Hypotension (Systolic Blood Pressure and/or Mean Blood Pressure less than the 5th percentile for age) * Abnormal Perfusion (2 or more of: abnormal capillary refill, tachycardia, decreased level of consciousness, decreased urine output) * Suspected or Confirmed Septic Shock (Shock due to Suspected or Confirmed Infectious Cause) * Patient has received initial fluid resuscitation of: Minimum of 40 mL/kg of isotonic crystalloid (0.9% Normal Saline and/or Ringer's Lactate) and/or colloid (5% albumin) as fluid boluses within the previous 6 hours for patients weighing less than 50 kg, OR Minimum of 2 litres (2000 mL) of isotonic crystalloid (0.9% Normal Saline and/or Ringer's Lactate) and/or colloid (5% albumin) as fluid boluses within the previous 6 hours for patients weighing 50 kg or more. * Patient has Fluid Refractory Septic Shock as defined by the Presence of all of 2a, 2b, and 2c.
Exclusion criteria
* Patient admitted to the Neonatal Intensive Care Unit (NICU) * Patient requiring resuscitation in the Operating Room (OR) or Post-Anesthetic Care Unit (PACU) * Full active resuscitative treatment not within the goals of care * Shock Secondary to Cause other than Sepsis (i.e. obvious signs of cardiogenic shock, anaphylactic shock, hemorrhagic shock, spinal shock) * Previous enrolment in this trial, where known by the research team
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in time to shock reversal | This outcome can be ascertained typically within 14 days of randomization | Difference (in hours) in time to shock reversal between the two study groups. Not available where death occurs while still in shock, or if the patient is placed on mechanical circulatory support for refractory shock. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measures of Organ Dysfunction - Pediatric logistic organ dysfunction score | 28 days | Pediatric logistic organ dysfunction score |
| Measures of Organ Dysfunction - Acute Kidney Injury | 28 days | Acute Kidney Injury |
| Measures of Organ Dysfunction - Ventilator Free Days | 28 days | Ventilator Free Days |
| Complications possibly attributable to fluid overload or third spacing of fluids - Soft tissue edema | Intervention Period (from randomization until shock is reversed; typically within 14 days) | Soft tissue edema |
| Complications possibly attributable to fluid overload or third spacing of fluids - Pulmonary edema | Intervention Period (from randomization until shock is reversed; typically within 14 days) | Pulmonary edema |
| Complications possibly attributable to fluid overload or third spacing of fluids - Pleural effusion requiring drainage | Intervention Period (from randomization until shock is reversed; typically within 14 days) | Pleural effusion requiring drainage |
| Complications possibly attributable to fluid overload or third spacing of fluids - Abdominal Compartment Syndrome | Intervention Period (from randomization until shock is reversed; typically within 14 days) | Abdominal Compartment Syndrome |
| Complications possibly attributable to inotrope/vasopressor use - Digital ischemia requiring revision amputation | 90 days | Digital ischemia requiring revision amputation |
| Complications possibly attributable to inotrope/vasopressor use - Clinical signs of digital tissue schema | Intervention Period (from randomization until shock is reversed; typically within 14 days) | Clinical signs of digital tissue schema |
| Complications possibly attributable to inotrope/vasopressor use - Clinical signs of compromised bowel perfusion | From randomization until 7 days after shock is reversed | Clinical signs of compromised bowel perfusion |
| Critical Care Treatments as binary measurement yes/no | Intervention Period (from randomization until shock is reversed; typically within 14 days) | Critical care treatments performed during intervention period. |
| Paediatric Intensive Care Unit Length of Stay | Up to 90 days | Paediatric Intensive Care Unit Length of Stay |
| Hospital Length of Stay | Up to 90 days | Hospital Length of Stay |
| Mortality Measures | 28-, 90- day, hospital mortality | Death |
| Health Service Outcomes - Paediatric Intensive Care Unit Admission Rate | 28 days | Paediatric Intensive Care Unit Admission Rate |
| Complications possibly attributable to fluid overload or third spacing of fluids - Diuretic Exposure | From randomization until 7 days after shock is reversed | Diuretic Exposure |
Countries
Canada
Outcome results
None listed