Hypertonic Saline: Bolus or Continuous Infusion
By Brian Gilbert, PharmD, BCPS, BCCCP
According to the
Centers for Disease
Control, it is estimated
that over 1.5 million
people sustain a
traumatic brain injury
(TBI) in the United
States each year.1
Treatment modalities
listed by the Brain Trauma Foundation
Guidelines (BTFG) include: decompressive
craniectomy, hyperosmolar therapy,
cerebrospinal fluid drainage, ventilation
techniques and anesthetics/analgesics/sedatives.2
Mannitol and hypertonic saline (HTS) make up
the majority of hyperosmolar therapies
practiced for treatment of TBI today. While
these agents have been used routinely for TBI
treatment, there remains a paucity of data on
agent superiority, administration schedules and
full understanding on their mechanisms of action
in the treatment of TBI. Each agent has pros and
cons associated with their use, and with the lack of
available evidence, the BTFG are unable to give
strong recommendations for either agent much less
dosing strategies. Current goals of therapy with
hypertonic saline are to manage elevated
intracranial pressures (ICP) and to maintain
cerebral perfusion pressures (CPP). Very little
evidence exists comparing the different dosing
strategies associated with HTS use. The focus of this
article will be examining the different dosing
strategies of utilizing hypertonic saline: bolus versus
continuous infusion
The Continuous hyperosmolar therapy for traumatic
brain-injured patients (COBI) trial (NCT03143751)
is an ongoing multicenter, randomized, controlled,
open-label, with blinded adjudication of primary
outcome trial, which will evaluate continuous
infusion HTS for a minimum of 48 hours in
moderate to severe TBI patients compared to
bolus dosing strategies.3 If patients meet inclusion
criteria then a bolus of HTS (7.5-15 g of 20 percent
depending on NaCl level) will be given to both
patient groups and then either stratified to continue
to receive bolus dosing of HTS or continuous
infusion 20 percent HTS through a central line. If
patients have elevations in ICP in the continuous
infusion HTS group, they will be permitted boluses of
HTS. The primary outcome will be long-term recovery
status as assessed by the Extended Glasgow Outcome Scale
questionnaire at six months. Hopefully, the COBI study
will shed some light on dosing strategies for HTS; however,
it will not give an answer as it pertains to mannitol bolus
dosing versus HTS.
The largest data set to date that has evaluated continuous
infusion HTS was done in 2011 by Roguilly et al.4 This was a
retrospective single-center cohort study in a surgical intensive
unit of a tertiary hospital. Fifty TBI patients with refractory
elevated ICP were treated with 20 percent HTS and dose
adjusted based off a pre-determined algorithm to a Na level
of 145 – 155 mmol/L for 7 days. Patients with elevated ICPs
were permitted to have mannitol boluses. There was a 9 mmHg
decrease in ICP the first hour of treatment (29 mmHg vs. 20
mmHg, p<0.05) and an increase in CPP, as well (61 mmHg vs. 67
mmHg, p<0.05). Na levels increased from 140 to 144 (p<0.05)
and plasma increased osmolality (275 vs. 290, p<0.05) within the
first hour of treatment. Hypercholeremia was the main adverse
effect seen; however, there was no associated acute kidney injury
or pontine myelinolysis observed. No rebound elevated ICP was
seen after discontinuation of the continuous HTS infusion.
This study was limited by its retrospective nature and small sample
size, but was one of the first to show that continuous infusion
HTS was a viable option for refractory elevated ICP who had failed
standard bolus therapy.
The only completed study to date that has evaluated continuous
infusion to bolus HTS therapy was performed by Maguigan et al
in 2017.5 This retrospective cohort analysis evaluated bolus versus
continuous infusion HTS in 162 severe TBI patients. The primary
outcome was median time to goal osmolality. Time to goal
osomolality was similar between bolus and continuous infusion
dosing strategies (9.78h vs. 11.4h; p=0.82). There was, however, a
significant difference in patients reaching goal osmolality, which
was in the continuous infusion group compared to bolus dosing
(93.9 percent vs. 73.3 percent, p=0.003). No difference was seen in
CCP, ICP, and length of stay or mortality between the two groups.
Currently, this is one of the only data sets that has compared
continuous infusion to bolus dosing for HTS in any capacity;
however, due to its small sample, size, retrospective study
design, and lack of real outcome associated data makes this
trial difficult to interpret. While goal osmolality is a good
surrogate marker and continuous infusion was more successful
at achieving it in this study, the lack of outcome associated data
makes it hard to draw any major conclusions.
There is relatively small retrospective data that suggests that HTS
may be a better option than mannitol as it pertains to elevated ICP
in TBI.4 Presently, there is not enough data present to show which
HTS dosing strategy should be utilized for elevated ICP in severe
TBI. With the COBI trial still underway, there will hopefully soon
be outcome data to better guide clinicians to support one strategy
or the other. For now, providers should base the decision whether
or not to implement a continuous infusion or bolus based strategy
on laboratory data, ICP/CPP values and total central access.
References
1. Rutland-Brown W, Langlois JA, Thomas KE, et al. Incidence
of traumatic brain injury in the United States, 2003. J Head
Trauma Rehabil. 2006; 21:544.
2. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the
Management of Severe Traumatic Brain Injury, Fourth
Edition. Neurosurgery. 2017 Jan 1;80(1):6-3)
3. Roquilly A, Lasocki S, Moyer JD, et al. COBI (COntinuous
hyperosmolar therapy for traumatic Brain-Injured patients)
trial protocol: a multicentre randomised open-label trial
with blinded adjudication of primary outcome. BMJ Open.
2017 Sep 24;7(9):e018035.
4. Roquilly A, Mahe PJ, Latte D, et al. Continuous controlledinfusion
of hypertonic saline solution in traumatic braininjured
patients: a 9-year retrospective study. Crit Care.
2011;15(5):R260.
5. Maguigan KL, Dennis BM, Hamblin SE, et al. Method of
Hypertonic Saline Administration: Effects on Osmolality
in Traumatic Brain Injury Patients. J Clin Neurosci. 2017
May;39:147-150.
PHARMACY
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