PHARMACY COLUMN
Table 1: Summary of major trials evaluating the use of crystalloids and/or hyperchloremia in critically ill patients
Trial Patient Population Study Design Study Groups Major Outcomes
Yunos et al
Multidisciplinary
JAMA 20121
ICU
(n=1,533)
Neurological
diagnosis (8%)
Prospective, open
label, sequential
period pilot study
CL (0.9% NaCl, 4%
gelatin, 4% albumin)
(n=760)
CR (Hartmann solution,
PL-148, chloride-poor
20% albumin)
(n=773)
Kidney injury and failure*:
CL 14% vs. CR 8.4%
(p <0.001)
RRT:
CL 10% vs. CR 6.3% (p=0.005)
ICU mortality:
CL 9% vs. CR 8% (p=0.42)
Young et al
JAMA 20154
(n=2,262)
Postsurgical (72%)
Neurological
operative admission
(3%)
Traumatic brain
injury (3%)
Double-blind,
cluster randomized,
double-crossover
0.9% NaCl
(n=1110)
PL-148
(n=1,152)
Kidney injury or failure*:
0.9% NaCl 9.2% vs. PL-148 9.6% (p=0.77)
RRT:
0.9% NaCl 3.3% vs. PL-148 3.4% (p=0.91)
ICU mortality:
0.9% NaCl 6.6% vs. PL-148 7.2% (p=0.62)
Semler et al
N Engl J Med5
2018
(n=15,802)
Five ICUs (medical,
cardiac, neurologic,
trauma, surgical)
Neuroscience ICU
(18%)
Traumatic brain
injury (9%)
Pragmatic,
unblended, cluster
randomized, multiple
crossover trial
0.9% NaCl
(n=7,860)
BC: PL-A or LR
(n=7,942)
^Major adverse kidney event within 30
days:
All cohort: 0.9% NaCl 15.4% vs. BC 14.3%
(p=0.04)
Neuroscience ICU: 0.9%NaCl 10.2% vs. BC
8.1% (p=0.04)
TBI: 0.9% NaCl 14% vs. BC 15% (p=0.58)
RRT:
0.9% NaCl 2.9% vs. BC 2.5% (p=0.08)
ICU mortality:
0.9% NaCl 7.3% vs. BC 6.6% (p=0.08)
Riha et al
Crit Care Med6
2017
(n=219)
Neurosciences ICUs
Intracerebral
hemorrhage
receiving continuous
3% hypertonic saline
Multicenter, retrospective,
propensitymatched
cohort
Hyperchloremia
(n=76)
Nonhyperchloremia
(n=143)
+AKI in propensity-matched cohort:
Hyperchloremia 34% vs. nonhyperchloremia
14%
(p=0.02)
In-hospital mortality in propensitymatched
cohort:
Hyperchloremia 34% vs. nonhyperchloremia
14%
(p=0.02)
Logistic regression analysis:
Hyperchloremia predicts in-hospital
mortality
(OR 4.4; 95% CI, 1.4-13.5)
Sadan et al
Crit Care Med7
2017
(n=1,267)
Subarachnoid
hemorrhage
Retrospective
analysis
#AKI
(n=1,055)
No AKI
(n=212)
In-hospital mortality:
AKI 28.3% vs. no AKI 6.1% (p<0.001)
Logistic regression analysis to evaluate for
risks for AKI:
10 mEq/L increase in mean serum chloride
(OR 7.39; 95% CI, 3.44-18.23)
CL: chloride liberal fluids; CR: chloride restricted fluids; PL-148: Plasma-Lyte 148; 0.9% NaCl: 0.9% sodium chloride; PL-A: Plasma-Lyte
A; LR: Lactated Ringer’s solution; BC: balanced crystalloids; TBI: traumatic brain injury
*Per RIFLE criteria; ^Composite of death from any cause, new renal replacement therapy or renal dysfunction,+per AKIN criteria, #per
KDIGO criteria
34