Sepsis, Septic Shock
Conditions
Brief summary
Despite evidence of the physiologic benefits and possible lower mortality associated with low chloride solutions, normal saline remains the most wildly used fluid in the world. Given uncertainty about the impact of lower chloride versus higher chloride solutions on mortality, it is unlikely that clinical practice will change without new and direct randomized controlled trial (RCT) evidence. Editorials published in leading critical care journals have called for RCT's to address this important clinical question. This trial will directly compare low chloride versus normal chloride for resuscitation in septic shock on patient-important outcomes such as mortality and AKI.
Detailed description
Severe infection can lead to many complications within the human body including low blood pressure, which is called septic shock. The main treatments for septic shock are intravenous antibiotics and intravenous fluid. There are many different intravenous fluids available for doctors to use. Each one of these fluids has potential advantages as well as potential disadvantages. Doctors will often look at many things when deciding which fluid to give including the results of bloodwork and the clinical characteristics of the patients themselves. There is limited direction from research studies that using one fluid type is better than another. Some preliminary research in the field has suggested that one specific electrolyte, call chloride, may be harmful when given to patients in high concentrations. Animal research has shown that the administration of high chloride fluids may be harmful to the lungs, kidneys, gastrointestinal and muscle cells. Some intravenous fluids have higher concentrations of chloride than others. The investigators plan to study the impact of giving patients with severe infection intravenous fluids with either a high chloride concentration (normal saline or high chloride albumin) or a low chloride concentration (Ringers Lactate or low chloride albumin). This trial will build on the earlier pilot, phase 1 study and will look at patient-important outcomes such as rate of death, kidney failure and length of stay in the ICU. This larger study has the potential to guide the care of critically ill patients with infection worldwide.
Interventions
Normal saline (chloride concentration 154 mmol/L)
Ringer's Lactate (chloride concentration 110 mmol/L)
Sponsors
McMaster University
The Physicians' Services Incorporated Foundation
Canadian Institutes of Health Research (CIHR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients 16 years or greater who meet all of the following: * require fluid resuscitation for refractory hypotension (systolic blood pressure \<90 mmHg or mean arterial blood pressure\<65 mmHg after 1 Litre bolus over 1 hour or less or organ hypo-perfusion (serum lactate \>4 mmol/L) * have a clinical suspicion of infection * are within 6 hours of hospital admission or critical care response team consultation * are anticipated to require ICU admission
Exclusion criteria
* intracranial bleed or intracranial hypertension during the index hospital admission * 10% of body surface area acute burn injury * bleeding/hemorrhage as likely cause of hypotension * a lack of commitment to life support * have previously enrolled in FISSH, or a confounding trial (e.g. a trial examining the effect of other intravenous fluids in septic shock patients) * been transferred from another hospital or facility \>6 hours since presentation to first hospital * pre-established end stage renal disease (ESRD) or are receiving hemodialysis (intermittent or continuous) at time of enrolment, or * been admitted to ICU directly from the operating room or post anaesthetic care unit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 30 day mortality | up to 30 days | Investigators expect that if a difference in survival is demonstrated that this will be evident within 30 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital mortality | up to 30 days | Investigators expect that if a difference in survival is demonstrated, that this will be evident within 30 days. |
| ICU mortality | up to 30 days | Investigators expect that if a difference in survival is demonstrated, that this will be evident within 30 days. |
| Hospital length of stay | up to 30 days | length of hospital stay up to 30 days |
| ICU length of stay | up to 30 days | length of ICU stay up to 30 days |
| Acute Kidney Injury | up to 30 days | Acute kidney injury - development of stage 2 or worse acute kidney injury (AKI) according to KDIGO guidelines17 based strictly on serum creatinine criteria. Stage 2 AKI is defined as serum creatinine 2.0-2.9 times baseline. For the purposes of analysis, baseline creatinine will be an outpatient reading within 365 days of the current admission date. If multiple pre-hospitalization values are available, the value closest to the date of hospital admission will be used. If an outpatient pre-hospitalization value is not available, the lowest creatinine value obtained during the current hospitalization will be considered baseline 18. |
| Ventilator free days | up to 30 days | defined as cumulative number of days alive without receiving greater than or equal to 2 hours of mechanical ventilation, censored at 30 days; patients who die prior to 30 days will be assigned -1 |
| Vasopressor-free days | up to 30 days | defined as the cumulative number of days alive without requiring greater than or equal to 2 hours of intravenous vasopressor support, censored at 30 days; patients who die prior to 30 days will be assigned -1 |
| Change in organ failure score | up to 30 days | calculated using the SOFA score (sequential organ failure assessments score) , defined as the net change in SOFA from day 1 until ICU discharge or death minimum 0, maximum 24 higher score is worse |
| hyperchloremia | up to 30 days | the number of patients with hyperchloremia |
| Hyperkalemia | up to 30 days | the number of patients with hyperkalemia |
| Hypernatremia | up to 30 days | the number of patients with hypernatremia |
| Acidosis | up to 30 days | the number of patients with acidosis |
| Serious adverse events related to study fluid | up to 30 days | critically ill patients are admitted to the ICU for life-sustaining therapies and medical complications are likely to occur in this population consistent with severity of illness. Due to these unique morbidity and mortality expectations, we don't collect generic adverse events but instead focus on study-related SAEs that the attending physician believes related to the study fluid with plausible time sequence and biological plausibility |
Countries
Canada, Saudi Arabia
Contacts
PRINCIPAL_INVESTIGATORBram Rochwerg, MSc,MD,FRCPC
McMaster University
Outcome results
None listed