Plasmalyte Versus Saline in Trauma Patients

Acute Kidney Injury Clinical Trial

— ASTRAU  

Official title:

Renal Effects of Fluid Resuscitation With Plasmalyte Viaflo Versus Saline in Trauma Patients (the ASTRAU Study)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03630224
• Other study ID #: P160919J
• Secondary ID: 2017-004206-17
• Status: Terminated
• Phase: Phase 3
• Start date: June 24, 2019
• Est. completion date: August 18, 2023

Study information

• Verified date: January 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Fluid resuscitation remains the cornerstone for the care of severe trauma patients to compensate for blood loss, to compensate for capillary leak induced by systemic inflammation but also to prevent the detrimental consequences of traumatic rhabdomyolysis. Isotonic saline (NaCl 0.9%), called "physiological serum" is the standard fluid for the resuscitation of severely injured patients. However, the formulation of NaCl 0.9% is not really physiological since its chloride concentration is 1.5 higher than the one of human plasma. This excessive chloride concentration leads to hyperchloremic acidosis and to a drop in renal perfusion after isotonic saline infusion. For this reason, we wonder whether fluid resuscitation with Plasmalyte would be beneficial for renal function of trauma patients in comparison with NaCl 0.9%. Our research question is:

In a population of trauma patients at high risk of acute kidney injury, does a fluid resuscitation with Plasmalyte Viaflo lower the incidence of severe acute kidney injury (stage 2 or 3 according to the KDIGO classification) compared with a resuscitation with isotonic saline (NaCl 0.9%)?

Description:

Fluid resuscitation remains the cornerstone for the care of severe trauma patients to compensate for blood loss, to compensate for capillary leak induced by systemic inflammation but also to prevent the detrimental consequences of traumatic rhabdomyolysis. Isotonic saline (NaCl 0.9%), called "physiological serum" is the standard fluid for the resuscitation of severely injured patients. However, the formulation of NaCl 0.9% is not really physiological since its chloride concentration is 1.5 higher than plasma. This excessive chloride concentration leads to hyperchloremic acidosis and to a drop in renal perfusion after isotonic saline infusion. A retrospective study conducted in the perioperative setting (abdominal surgery) reported a significant decrease in mortality and acute kidney injury in 926 patients receiving balanced crystalloid solution compared to a propensity-matched population of 2778 patients receiving isotonic saline. Yunos et al. conducted a prospective sequential period study including 760 patients receiving chloride-rich solution during the first 6-month period and 773 patients receiving chloride-poor solution during the next 6-month period. They reported a decrease in severe acute kidney injury (I or F in the RIFLE classification) in the group receiving chloride-poor solution. Large retrospective studies in intensive care confirmed a beneficial effect of the use of chloride-poor solutions on survival compared to chloride-rich solutions. A recent meta-analysis including 5 small size randomized controlled trials, 1 controlled trial and two retrospective studies, reported also a decrease in acute kidney injury. A recent multicenter study randomized 2778 patients to receive either Plasmalyte 148 or NaCl 0.9% during their ICU stay. No AKI or mortality differences were reported. However, this study included patients with low ICU severity score (mean APACHE II = 14) and at low risk of severe AKI (severe AKI incidence = 9%). Moreover, they received a median amount of fluid of 2000 mL during their ICU stay. This small fluid volume may not be enough to show any difference between rich-chloride and poor-chloride solutions on AKI in this population with low ICU severity scores.

Trauma patients are particularly at risk of AKI during the acute phase of trauma because of hypovolemia (bleeding), rhabdomyolysis and systemic inflammation (traumatic tissue injuries and emergency surgeries). AKI is reported in 18 to 26 % of trauma patients. In our database (TraumaBase®, traumabase.eu) that included at the time of the study the 6 trauma centers of the Paris area (France), we reported a 24% incidence of severe AKI (stage I or F of the RIFLE classification) in the subpopulation of patients needing at least one red blood cell unit transfusion in the 6 first hours of care. Moreover, this subpopulation receives an average amount of 6000 mL of fluid during the first 24 hours of care. We postulate that trauma patients at high risk of AKI receiving high volume of fluid can be the best population target to demonstrate a beneficial effect of Plasmalyte vs isotonic saline on severe AKI occurrence in a prospective, blinded, randomized manner.

Thus, we formulate the following hypothesis:

In a population of trauma patients, at high risk of AKI, a fluid resuscitation with Plasmalyte Viaflo during the 5 first days of care will lower decrease the incidence of severe acute kidney injury (stage 2 or 3 according to the KDIGO classification) compared with a resuscitation with isotonic saline (NaCl 0.9%)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 365
• Est. completion date: August 18, 2023
• Est. primary completion date: August 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Severe trauma defined by at least one Vittel criteria

• Prescription for at least one red blood cell unit transfusion within 6 hours after trauma

• Delay between trauma and study randomization = 6 hours

• Patient able to give consent or included in emergency situation

• Patient affiliated to Health security system

Exclusion Criteria:

• Age < 18 years

• Chronic kidney disease needing requiring renal replacement therapy

• Participation to another interventional trial interacting with renal function or which requires the use of a fluid resuscitation

• Fluid resuscitation > 4000 mL before inclusion

Related Conditions & MeSH terms

• Acute Kidney Injury
• Severe Trauma Patients
• Wounds and Injuries

Intervention

Drug:
• Plasmalyte Viaflo
Intervention description: fluid resuscitation using exclusively Plasmalyte up to 20L during the first 5 days
• NaCl 0.9%
Intervention name: NaCl 0.9% Intervention description: fluid resuscitation using exclusively NaCl 0.9% up to 20L during the first 5 days

Locations

Country	Name	City	State
France	Département d'Anesthésie Réanimation - Kremlin Bicêtre	Le Kremlin-Bicêtre

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (10)

Bagshaw SM, George C, Gibney RT, Bellomo R. A multi-center evaluation of early acute kidney injury in critically ill trauma patients. Ren Fail. 2008;30(6):581-9. doi: 10.1080/08860220802134649. — View Citation

Bihorac A, Delano MJ, Schold JD, Lopez MC, Nathens AB, Maier RV, Layon AJ, Baker HV, Moldawer LL. Incidence, clinical predictors, genomics, and outcome of acute kidney injury among trauma patients. Ann Surg. 2010 Jul;252(1):158-65. doi: 10.1097/SLA.0b013e3181deb6bc. — View Citation

Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte(R) 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2012 Jul;256(1):18-24. doi: 10.1097/SLA.0b013e318256be72. Erratum In: Ann Surg. 2013 Dec;258(6):1118. — View Citation

Krajewski ML, Raghunathan K, Paluszkiewicz SM, Schermer CR, Shaw AD. Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation. Br J Surg. 2015 Jan;102(1):24-36. doi: 10.1002/bjs.9651. Epub 2014 Oct 30. — View Citation

Raghunathan K, Shaw A, Nathanson B, Sturmer T, Brookhart A, Stefan MS, Setoguchi S, Beadles C, Lindenauer PK. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis*. Crit Care Med. 2014 Jul;42(7):1585-91. doi: 10.1097/CCM.0000000000000305. — View Citation

Shaw AD, Bagshaw SM, Goldstein SL, Scherer LA, Duan M, Schermer CR, Kellum JA. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg. 2012 May;255(5):821-9. doi: 10.1097/SLA.0b013e31825074f5. — View Citation

Shaw AD, Raghunathan K, Peyerl FW, Munson SH, Paluszkiewicz SM, Schermer CR. Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS. Intensive Care Med. 2014 Dec;40(12):1897-905. doi: 10.1007/s00134-014-3505-3. Epub 2014 Oct 8. — View Citation

Shaw AD, Schermer CR, Lobo DN, Munson SH, Khangulov V, Hayashida DK, Kellum JA. Impact of intravenous fluid composition on outcomes in patients with systemic inflammatory response syndrome. Crit Care. 2015 Sep 12;19(1):334. doi: 10.1186/s13054-015-1045-z. Erratum In: Crit Care. 2016;20:17. — View Citation

Young P, Bailey M, Beasley R, Henderson S, Mackle D, McArthur C, McGuinness S, Mehrtens J, Myburgh J, Psirides A, Reddy S, Bellomo R; SPLIT Investigators; ANZICS CTG. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial. JAMA. 2015 Oct 27;314(16):1701-10. doi: 10.1001/jama.2015.12334. Erratum In: JAMA. 2015 Dec 15;314(23):2570. — View Citation

Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012 Oct 17;308(15):1566-72. doi: 10.1001/jama.2012.13356. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Acute Kidney Injury (stage 2 or 3 according to KDIGO classification) over the 5 first days after trauma		over the 5 first days after trauma
Secondary	Proportion of patients requiring renal replacement therapy (during 28 days)		during 28 days
Secondary	Amount of transfused blood product units (during the first 5 days)		during the first 5 days
Secondary	Number of days alive without free of mechanical ventilation (during 28 days)		during 28 days
Secondary	Days spent alive outside the ICU (during 28 days)		during 28 days
Secondary	Mortality		at 28 days
Secondary	Difference between the serum creatinine peak in the 5 first days of ICU stay and the baseline creatinine		during the 5 first days