Balanced Solutions and Plasma Electrolytes

Critical Illness Clinical Trial

— BASE  

Official title:

Balanced Solutions and Plasma Electrolytes in the Medical Intensive Care Unit

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03537898
• Other study ID #: 180397
• Status: Completed
• Phase: N/A
• Start date: June 1, 2018
• Est. completion date: March 2, 2019

Study information

• Verified date: October 2019
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The administration of intravenous fluids is ubiquitous in the care of the critically ill. Commonly available isotonic crystalloid solutions contain a broad spectrum electrolyte compositions including a range chloride concentrations. Recent prospective, randomized trials have shown improved patient outcomes with the use of balanced crystalloids compared to saline. There have not been large randomized studies comparing acetate buffered balanced crystalloids to non-acetate buffered balanced crystalloids in the critically ill. BASE will be a pilot study for a large, cluster-randomized, multiple-crossover trial enrolling critically ill patients from the Medical ICU at Vanderbilt University from June 2018 until January 2019. The primary endpoint will be plasma bicarbonate concentration between Intensive Care Unit admission and hospital discharge.

Description:

BASE is a pilot, cluster-randomized, multiple-crossover trial of lactated Ringer's versus Normosol-R pH 7.4 with regard to plasma bicarbonate concentration between intensive care unit admission and hospital discharge among all patients admitted to the medical intensive care unit. Between June 2018 and January 2019, all patients admitted to the medical intensive care unit at Vanderbilt University Medical Center who are 18 years or older will be enrolled. The study will occur in one-month blocks. The medical intensive care unit (MICU) will be randomized to an initial fluid group (lactated Ringer's or Normosol). The assigned fluid will be used exclusively for all patients receiving isotonic crystalloid for the duration of the month-long block (except in the presence of pre-specified contraindications). The assigned study fluid will switch at the end of each month-long block such that half of hte months are assigned to lactated Ringer's and half of the months are assigned to Normosol-R pH 7.4. It is anticipated that around 2,000 patients will be enrolled from the medical ICU during the study period. The primary outcome analysis will be an intention-to-treat comparison of the primary outcome of bicarbonate concentration (mmol/L) between enrollment and 7 days after enrollment between the lactated Ringer's and Normosol-R groups using generalized estimating equations with a random effect for study period and accounting for repeated measures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2093
• Est. completion date: March 2, 2019
• Est. primary completion date: February 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients admitted to the Medical ICU during the study period (Enrolled patients who are discharged from the hospital are eligible again if they are readmitted to the Medical ICU during the study period)

Exclusion Criteria:

• Age < 18 years old

• Prisoners

Related Conditions & MeSH terms

• Acidosis
• Acidosis, Metabolic
• Critical Illness

Intervention

Other:
• Lactated Ringer's
Lactated Ringer's will be used whenever an isotonic crystalloid is ordered
• Normosol
Normosol-R pH 7.4 will be used whenever an isotonic crystalloid is ordered

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (8)

Finfer S, Liu B, Taylor C, Bellomo R, Billot L, Cook D, Du B, McArthur C, Myburgh J; SAFE TRIPS Investigators. Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care. 2010;14(5):R185. doi: 10.1186/cc9293. Epub 2010 Oct 15. — View Citation

Hadimioglu N, Saadawy I, Saglam T, Ertug Z, Dinckan A. The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation. Anesth Analg. 2008 Jul;107(1):264-9. doi: 10.1213/ane.0b013e3181732d64. — View Citation

Hasman H, Cinar O, Uzun A, Cevik E, Jay L, Comert B. A randomized clinical trial comparing the effect of rapidly infused crystalloids on acid-base status in dehydrated patients in the emergency department. Int J Med Sci. 2012;9(1):59-64. Epub 2011 Nov 23. — View Citation

Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, Slovis CM, Lindsell CJ, Ehrenfeld JM, Siew ED, Shaw AD, Bernard GR, Rice TW; SALT-ED Investigators. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):819-828. doi: 10.1056/NEJMoa1711586. Epub 2018 Feb 27. — View Citation

Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):829-839. doi: 10.1056/NEJMoa1711584. Epub 2018 Feb 27. — View Citation

Shin WJ, Kim YK, Bang JY, Cho SK, Han SM, Hwang GS. Lactate and liver function tests after living donor right hepatectomy: a comparison of solutions with and without lactate. Acta Anaesthesiol Scand. 2011 May;55(5):558-64. doi: 10.1111/j.1399-6576.2011.02398.x. Epub 2011 Feb 22. — View Citation

Weinberg L, Chiam E, Hooper J, Liskaser F, Hawkins AK, Massie D, Ellis A, Tan CO, Story D, Bellomo R. Plasma-Lyte 148 vs. Hartmann's solution for cardiopulmonary bypass pump prime: a prospective double-blind randomized trial. Perfusion. 2018 May;33(4):310-319. doi: 10.1177/0267659117742479. Epub 2017 Nov 16. — View Citation

Weinberg L, Pearce B, Sullivan R, Siu L, Scurrah N, Tan C, Backstrom M, Nikfarjam M, McNicol L, Story D, Christophi C, Bellomo R. The effects of plasmalyte-148 vs. Hartmann's solution during major liver resection: a multicentre, double-blind, randomized controlled trial. Minerva Anestesiol. 2015 Dec;81(12):1288-97. Epub 2014 Nov 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Bicarbonate Concentration	The primary outcome is a repeated measures variable of plasma bicarbonate concentration (mmol/L) between ICU admission and 7 days.	Between ICU admission and Day 7
Secondary	Plasma Bicarbonate Concentration < 20 mmol/L		Between ICU admission and Day 7
Secondary	Lowest Plasma Bicarbonate Concentration		Between ICU admission and Day 7
Secondary	Plasma Chloride Concentration > 110 mmol/L		Between ICU admission and Day 7
Secondary	Plasma Chloride Concentration < 100 mmol/L		Between ICU admission and Day 7
Secondary	Highest Plasma Chloride Concentration		Between ICU admission and Day 7
Secondary	Change in Plasma Chloride Concentration from Baseline to Peak		Between ICU admission and Day 7
Secondary	Plasma Sodium Concentration > 145 mmol/L		Between ICU admission and Day 7
Secondary	Plasma Sodium Concentration < 135 mmol/L		Between ICU admission and Day 7
Secondary	Plasma Potassium Concentration > 5.5 mmol/L		Between ICU admission and Day 7
Secondary	Plasma values for Sodium, Potassium, Chloride, Bicarbonate, Blood Urea Nitrogen, Creatinine, Calcium, and Lactate		Between ICU admission and Hospital Discharge or 30 Days
Secondary	Strong Ion Difference	(Sodium + Potassium + Calcium) - (Chloride + Lactate) in mmol/L	Between ICU admission and Day 7
Secondary	Arterial pH		Between ICU admission and Day 7
Secondary	Arterial Standard Base Excess		Between ICU admission and Day 7
Secondary	Major Adverse Kidney Events within 30 days	This composite outcome will be considered present if at least one of the following occur: (1) A patient dies prior to the earlier of hospital discharge or day 30; (2) A patient receives new renal replacement therapy between enrollment and day 30, or (3) A patient has persistent renal dysfunction at the earlier of hospital discharge or day 30 (persistent renal dysfunction is defined as = 200% of creatinine from baseline)	30 Days after Enrollment Censored at Hospital Discharge
Secondary	30-Day In-Hospital Mortality		30 Days after Enrollment Censored at Hospital Discharge
Secondary	New Renal Replacement Therapy	The initiation of any renal replacement therapy between enrollment and 30 days censored at hospital discharge in a patient not known to have previously received renal replacement therapy.	30 Days after Enrollment Censored at Hospital Discharge
Secondary	Stage II or Higher Acute Kidney Injury	A patient will meet this outcome if they meet Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria for stage II acute kidney injury or higher	Between ICU admission and Day 7
Secondary	Persistent Renal Dysfunction	Final creatinine value before discharge or 30 days after enrollment = 200% of baseline creatinine.	30 Days after Enrollment Censored at Hospital Discharge
Secondary	Total Volume of Blood Product Transfusion		Between ICU admission and Day 7
Secondary	Dose of Vasopressor	Dose of vasopressor (in norepinephrine equivalents, µg/kg/min)	Between ICU admission and Day 7
Secondary	Intensive Care Unit-Free Days	Intensive care unit-free days to day 28 (ICU-free days) will be defined as the number of days from the time of the patient's physical transfer out of the ICU until day 28 after enrollment. Patients who die prior to day 28 after enrollment received a value of 0 for ICU-free days. Patients who never transfer out of the ICU prior to day 28 after enrollment will receive a value of 0 for ICU-free days. Patients who transferred out of the ICU, return to the ICU, and are not subsequently transferred out of the ICU again before day 28 after enrollment will receive a value of 0 for ICU-free days. For patients who transfer out of the ICU, are readmitted to the ICU, and subsequently transfer out of the ICU again prior to day 28 after enrollment, ICU-free days will be awarded based on the time of the final transfer out of the ICU prior to day 28 after enrollment.	Between ICU admission and Day 28
Secondary	Vasopressor-Free Days	Vasopressor-free days to day 28 will be defined as the number of days from the time of vasopressor cessation until day 28 after enrollment. Patients who die prior to day 28 after enrollment will receive a value of 0 for vasopressor-free days. Patients who never cease to receive vasopressors prior to day 28 after enrollment receive a value of 0 for vasopressor-free days. Patients who achieve vasopressor cessation, return to receiving vasopressors, and do not again achieve vasopressor cessation before day 28 after enrollment receive a value of 0 for vasopressor-free days. For patients who achieve vasopressor cessation, return to receiving vasopressors, and subsequently achieve cessation of vasopressors again prior to day 28 after enrollment, vasopressor-free days will be awarded based on the time of the final cessation of vasopressors prior to day 28 after enrollment. Survivors who never receive vasopressors received 28 vasopressor-free days.	Between ICU admission and Day 28
Secondary	Renal Replacement Therapy-Free Days	Renal replacement therapy-free days to day 28 (RRT- free days) will be defined as the number of days from the time of the final RRT treatment until day 28 after enrollment. Patients who die prior to day 28 after enrollment receive a value of 0 for RRT-free days. Patients who continue to receive RRT through day 28 after enrollment receive a value of 0 for RRT-free days. Patients who achieve RRT cessation, return to receiving RRT, and do not again achieve RRT cessation before day 28 after enrollment receive a value of 0 for RRT-free days. For patients who achieve RRT cessation, return to receiving RRT, and subsequently achieve cessation of RRT again prior to day 28 after enrollment, RRT-free days will be awarded based on the time of the final RRT treatment prior to day 28 after enrollment. Survivors who never receive RRT will be awarded 28 RRT-free days.	Between ICU admission and Day 28
Secondary	Ventilator-Free Days	Ventilator-free days to day 28 (VFDs) will be defined as the number of days from the time of initiating unassisted breathing (breathing without support of the mechanical ventilator) until day 28 after enrollment. Patients who die prior to day 28 after enrollment will receive a value of 0 for VFDs. Patients who never achieve unassisted breathing prior to day 28 after enrollment will receive a value of 0 for VFDs. Patients who achieve unassisted breathing, returned to assisted breathing, and do not again achieve unassisted breathing before day 28 after enrollment will receive a value of 0 for VFDs. For patients who achieve unassisted breathing, return to assisted breathing, and subsequently achieve unassisted breathing again prior to day 28 after enrollment, VFDs will be awarded based on the time of the final initiation of unassisted breathing prior to day 28 after enrollment. Survivors who never experience assisted breathing will receive 28 VFDs.	Between ICU admission and Day 28