Evidence Based Medicine:

Wisit Cheungpasitporn, MD.PGY-3, Internal Medicine

“Normal Saline is Bad”

Normal Saline is not Normal?

• May induce or exacerbate: – hyperchloremia and metabolic acidosis – renal vasoconstriction and decreased glomerular

filtration rate (GFR)– prolong time to first micturition– decrease urine output in major surgery.

JAMA. 1970;214(9):1710

Crit Care Resusc. 2011;13(4):262-270

• 2 L of saline decreased cortical perfusion in human study participants compared with Plasma-Lyte

Do patients in ICU Chloride-Restrictive IV fluids

Chloride-Liberal IV fluids

-Acute Kidney Injury-ICU and hospital survival

Method

• A prospective, open-label, before-and-after pilot study in the 22-bed ICU.

• The Austin Hospital, a tertiary care hospital affiliated with the University of Melbourne.

• Control period: February 18 to August 17, 2008

• Intervention period: February 18 to August 17, 2009.

Method

• Control period: IV fluids were given according to clinician preferences with free use of Chloride-rich fluids. – 0.9% saline (chloride concentration: 150 mmol/L)

(Baxter Pty Ltd)– 4% succinylated gelatin solution (chloride

concentration: 120 mmol/L) (Gelofusine, BBraun) – 4% albumin in sodium chloride (chloride

concentration: 128 mmol/L) (4% Albumex, CSL Bioplasma).

Method

• Following a 6-month phase-out period that included education and preparation of all ICU staff and logistic arrangements for fluid accountability and delivery.

• No additional training was provided to nursing or medical staff.

Method

• The intervention period: Chloride-Restrictive IV fluids– lactated crystalloid solution (chloride

concentration: 109 mmol/L) (Hartmann solution, Baxter Pty Ltd)

– A balanced buffered solution (chloride concentration: 98 mmol/L) (Plasma-Lyte 148, Baxter Pty)

– A 20% albumin solution (chloride concentration: 19 mmol/L) (20% Albumex, CSL Bioplasma).

• The intervention period:– Chloride-rich fluids available only after

prescription by the attending for specific conditions (eg, hyponatremia, traumatic brain injury, and cerebral edema).

– Similar fluid changes were instituted in the ED but not in the OR or general wards.

Method

• Collected data on– Age, sex, APACHE II and III scores, SAPS II, and multiple

clinical characteristics. – pre-ICU admission serum Cr levels and daily Cr during

ICU admission. – RRT, excluding pts with preexisting ESRD on long-term

dialysis and RRT for drug toxicity.– In RRT-treated survivors of ICU stay, data on dialysis

status at 3 mths after discharge were obtained. – RRT was initiated according to the criteria of the

Randomised Evaluation of Normal vs Augmented Level (RENAL) Replacement Therapy in ICU Trial.

Method

• Primary outcomes: – increase in Cr from baseline to peak ICU level and

incidence of AKI according to the risk, injury, failure, loss, end-stage (RIFLE) system definitions.

• Secondary post hoc analysis outcomes:– the need for RRT– length of stay in ICU and hospital– survival.

Method

RIFLE criteria

• The RIFLE criteria was put forward by the Acute Dialysis Quality Initiative (ADQI) in 2005.

The AKIN "Acute Kidney Injury Network" criteria were published in 2007 after a meeting in the Netherlands comprised of multiple experts on AKI.

Method

• Baseline Cr: the lowest Cr available in the 1-month period prior to ICU admission.

• If not available, Cr was estimated using the MDRD equation (assuming a lower limit of normal baseline GFR of 75 mL/min).

Statistical Analysis

• All statistical analysis was performed using Stata version 11 (StataCorp) and SAS version 9.2 (SAS Institute).

• Baseline comparisons were performed using χ2 tests for equal proportion.

• Continuously normally distributed variables were compared using t tests.

• Non–normally distributed data were compared using Wilcoxon rank sum tests.

• The increase in Cr from ICU admission to peak level was analyzed using generalized linear modeling.

• AKI and the need for RRT were analyzed using logistic regression.

• Time-to-event analysis was performed using Cox proportional hazard modeling with results reported as HRs with 95% CIs and presented as Kaplan-Meier curves.

• Comparisons between survival curves were performed using log-rank tests.

Statistical Analysis

• Multivariable sensitivity analysis was performed on all outcomes, adjusting for covariates of sex, APACHE III score, diagnosis, operative status, admission type (elective or emergency) and baseline Cr.

Statistical Analysis

• Subgroup analyses according to time in ICU, APACHE score, risk of death, presence of sepsis, and cardiac surgery.

• Assessed all outcome variables after excluding pts in whom baseline Cr was not known.

• To reduce the chance of a type I error due to reporting multiple outcomes, a 2-sided P value of .01 was used to indicate statistical significance.

Statistical Analysis

Results

Results

• Patients received less chloride: 694–>496 mmol/patient.

• Average Cr rose by 0.25 mg/dL per pt in control period — but only by 0.17 mg/dL in the intervention period during ICU stay before adjustment (22.6 vs. 14.8 μmol/l; P=0.03; adjusted P=0.07).

Results

• 10% of pts needed RRT during control v.s. 6.3% during intervention period (p = .005).

• After adjustment for covariates, this association remained for incidence of injury and failure class of RIFLE-defined AKI (OR, 0.52 [95% CI, 0.35-0.75]; p<.001) and use of RRT (OR, 0.52 [95% CI, 0.33-0.81]; p = .004).

Results

• No differences in mortality, hospital or ICU length of stay or need for long-term dialysis requirements .

Conclusion

• The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT.

Strengths and Limitations

• This study raises very important questions on the safety of chloride-rich solutions and might lead to important changes in our fluid resuscitation strategies.

• One Center• Not randomized/Not Blind• The intervention was of bundle-of-care kind

(Hawthorne effect) • Heterogeneity of IV fluids

Strengths and Limitations

• Is IV fluid with bicarb(?cost) better than Saline?

• Cost?• Future prospective trials have to confirm the

findings.

Special Thanks to: • Dr. Knight ; my EBM preceptor and fly fishing

master