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The fluids used for hydration and resuscitation contain supraphysiological concentrations of chloride induce or exacerbate hyperchloremia and metabolic acidosis cause renal vasoconstriction and decreased glomerular filtration rate (GFR) prolong time to first micturition and decrease urine output in major surgery
METHODS Prospective, open label, before-and-after pilot study 22-bed multidisciplinary ICU of the Austin Hospital, a tertiary care hospital affiliated with the University of Melbourne.
Period division Control period: February 18 to August 17, 2008 Phase-out period : August 18, 2008, to February 17, 2009 Intervention period: February 18 to August 17, 2009
Control period The intravenous fluids were given according to clinician preferences with free use of chloride-rich fluids: Chloride-rich fluids Cl (mmol) Brand of product 0.9% saline 150 Baxter Pty Ltd 4% succinylated gelatin solution 120 Gelofusine, Bbraun 4% albumin in sodium chloride 128 4% Albumex, CSL Bioplasma
Phase-out period education and preparation education and preparation of all ICU staff and logistic arrangements for fluid accountability and delivery, the intervention period commenced with enrollment of all consecutive admissions in the next 6 months.
Intervention period Chloride-rich fluids (0.9% saline, 4% succinylated gelatin solution, or 4% albumin solution) were now made available only after prescription by the attending specialist for specific conditions: Hyponatremia traumatic brain injury cerebral edema
Other fluid offered Chloride restrictive fluid Cl (mmol/l) Brand of product Lactated crystalloid solution Balanced buffered solution 109 98 20% albumin solution 19 Hartmann solution, Baxter Pty Ltd Plasma-Lyte 148, Baxter Pty 20% Albumex, CSL Bioplasma
Characteristic age, sex, (APACHE) II and III scores, Simplified Acute Physiology Score II (SAPS II) pre-icu admission serum creatinine levels and daily morning creatinine levels RRT-treated survivors of ICU stay, and dialysis status at 3 months after ICU discharge Renal replacement therapy was initiated according to the criteria of the Randomised Evaluation of Normal vs Augmented Level (RENAL)
Analyzed creatinine level RIFLE criteria The baseline creatinine level was based on the lowest creatinine level available in the 1-month period prior to ICU admission Creatinine level was estimated using the Modification of Diet in Renal Disease (MDRD) equation (assuming a lower limit of normal baseline GFR of 75 ml/min).
Statistical analysis To explore the biological plausibility of our findings, we assessed the relationship between chloride intake and changes in serum creatinine level in a nested cohort of 100 patients during each period in which detailed fluid data were obtained
RESULT Control period: 760 patient Intervention period: 773 patient Median follow-up time: 11 days There were no significant differences with regard to: Age Sex baseline creatinine level APACHE scores SAPS II Comorbidities diagnostic groups types of admission
Composition of trail fluids
Changes in fluid therapy and electrolytes Control Intervention Status Saline 2411L (3.2/patient) 52L (0.06/patient) (P<0.01) 4% gelation 538L (0.7/patient) 0L (0/patient) (P<0.01) 4% Albumin 269L (0.35/patient) 80L (0.1/patient) (P<0.01) Hartmann solution 469L (0.6/patient) 3205L (4.1/patient) (P<0.01) Plasma-Lyte 65L (0.08/patient) 160L (0.2/patient) (P=0.04) 20% Albumin 87L (0.1/patient) 268L (0.35/patient) (P<0.01) Chloride 649mmol/patient 496mmol/patient Sodium 750mmol/patient 623mmol/patient Potassium 3.5mmol/patient 22mmol/patient Lactate 18mmol/patient 120mmol/patient Serum Creatinine 22.6μmol/L 14.8μmol/L
Incidence of Acute kidney injury
Development of stage 2 or 3 AKI in ICU
Renal replacement therapy in ICU
Mortality and hospitalization Mortality in ICU 65 patient ( 9%; 95% CI, 7%- 11%) Mortality in hospital 112 patient (15%; 95% CI, 12%-17%) Median ICU length of stay Median hospital length of stay Patients who survived to ICU discharge after being treated with RRT Control Intervention P value 42.9 hours (IQR, 21.1-88.6 hours) 11 days (IQR, 7-21 days) 6 patients (12%; 95% CI, 3%-21%) 59 patient (8%; 95% CI, 6%-10%) 102 patient (13%; 95% CI, 11%-16%) 42.8 hours (IQR, 21.8-90.5 hours) 11 days (IQR, 7-22 days) 5 patients (15%; 95% CI, 3%-27%) P=0.42 P=0.44 P=0.52 P=0.57 P=0.95
COMMENT A controlled before-and after study to compare the renal functional changes Chloride restrictive intravenous fluid strategy was associated with a significant reduction in the increase of mean creatinine level from baseline to peak ICU level a significant decrease in the incidence of AKI and the use of RRT
Comparison with previous studies Controlled human studies the shorter time to micturition, greater urine output, and better renal cortical perfusion 30 000 surgical patients saline therapy increases the risk of patients requiring acute dialysis compared with Plasma-Lyte administration
Pathophysiology Greater chloride delivery to the macula densa activate the tubulo glomerular feedback: trigger afferent arteriolar vasoconstriction, mesangial contraction, and associated reductions in GFR Chloride infusion may induce thromboxane release with associated vasoconstriction enhanced responsiveness to vasoconstrictor agents: Angiotensin II receptor blockers
Gelatin solution 2 randomized controlled studies in critically ill patients reporting renal outcomes: 1. AKI was significantly lower with a gelatin solution compared with a starch solution 2.Compared a gelatin solution with 4.5% albumin: no difference in the incidence of acute renal failure A meta-analysis found that gelatin solutions actually decreased the risk of AKI Removing a gelatin solution alone may have been responsible for the findings
Albumin Fluid Evaluation (SAFE) trial Resuscitation with 4% albumin was compared with saline: no differences in renal outcomes were found classic Guytonian physiological studies hyperoncotic albumin increases renin secretion, markedly decreases urine flow rate and electrolyte excretion, and leads to either no change or a small decrease in GFR Prospective cohort study the use of hyperoncotic albumin was associated OR of 5.99 for the occurrence of a renal event Effect of 20% albumin on the kidney remains unclear
Strengths and limitations The study was not a blinded randomized trial Practically impossible to blind a bundle of care involving 6 different types of fluid before-and after bundle-of-care studies involving complex care in acutely ill patients. Assessment for baseline renal function is problematic and of limited accuracy, using the MDRD equation excluding all patients in MDRD equation used, the results remained unchanged
Strengths and limitations The 2 study periods enrolled patients during the same time of the year, ruling out a seasonal effect There are potential risks associated with restricting chloride-rich fluids and more isotonic fluids in Hyponatremia Alkalemia cerebral edema traumatic brain injury
Future studies The findings need to be confirmed in different health care systems and different ICUs
CONCLUSION Restricting intravenous chloride intake was associated with a significant decrease in the incidence of AKI and the use of RRT
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Supplemental study To explore the biological plausibility of our findings, we assessed the relationship between chloride intake and changes in serum creatinine level in a nested cohort of 100 patients during each period in which detailed fluid data were obtained
Time-to-event analysis was performed using Cox proportional hazard modeling with results reported as hazard ratios (HRs) with 95% confidence intervals and presented as Kaplan-Meier curves. Comparisons between survival curves were performed using logrank tests.
Significant differences by log-rank test were evident in time-to-first event curves of injury and failure class of RIFLE-defined AKI (P.001; FIGURE 1) and RRT use (P=.004; FIGURE 2).