The study's aim is to ascertain the best approach for providing sedation and pain
management for patients who have sustained trauma and are requiring respiratory support
from a mechanical ventilator. The common approach to patients who need mechanical
ventilation is to provide continuous drips of sedatives and pain medicine and awaken the
patient once a day to check the brain functions. Another approach is to provide pain
medicine and reserve sedatives for only a short duration when needed. The difference
between approaches has not been studied in Trauma patients.

Analgesia-First Sedation in Trauma Patients

Mechanical Ventilation

Respiratory Failure

A significant proportion of patients admitted to the intensive care unit (ICU) require
mechanical ventilation (MV). To facilitate care and maintain comfort for patients
requiring MV, the utilization of a large quantity of sedatives and analgesics is required
with either continuous infusion or intermittent dosing. However, prolonged continuous
administration of sedatives and analgesics can contribute to prolonged MV. Numerous
studies have shown that instituting protocol-directed sedation (PDS) by continuous
infusion of sedatives and analgesics using a protocol that includes a daily interruption
(DI) of the sedative will improve MV outcomes, specifically the duration of MV.

Protocol-directed sedation and daily sedation interruption:

Brook AD et al. performed a randomized, single-center, clinical trial; comparing
protocol-directed sedation versus non-protocol-directed sedation in 321 mechanically
ventilated patients. They included patients greater than the age of who were admitted to
the medical intensive care unit. Based on randomization, 162 patients received
protocol-directed sedation and 159 patients received non-protocol-directed sedation. The
primary outcome measure was the duration of mechanical ventilation and secondary outcomes
included: the length of ICU and hospital stay. The results revealed a reduction in the
mean duration of mechanical ventilation for the protocol-directed sedation group (89.1 ±
133.6 hrs vs. 124.0 ± 153.6 hrs; p = .003). In addition, the protocol-directed sedation
group had a reduced length of stay in the intensive care unit and hospital {5.7 ± 5.9
days vs. 7.5 ± 6.5 days (p = .013) and 14.0 ± 17.3 days vs. 19.9 ± 24.2 days (p < .001);
respectively}. The protocol-directed sedation group (n = 66) had a reduced duration of
continuous intravenous sedation (3.5 ± 4.0 days vs. 5.6 ± 6.4 days; p = .003). Brook's
study demonstrated the clinical benefits of having protocol-directed or nurse-directed
sedation in the medical intensive care unit. Since the study only involved patients in
the medical intensive care unit, it is uncertain if the results are applicable to
patients in the surgical unit.

Kress JP, et al. performed a randomized, single-center, clinical trial to evaluate daily
interruption of continuous infusion of sedation in 128 mechanically ventilated adult
patients. Notable exclusion criteria included patients already on sedative agents upon
transfer to the ICU and admission due to resuscitation from cardiac arrest. The primary
endpoints of the study included: the duration of mechanical ventilation, the length of
stay in the intensive care unit, and the length of stay in the hospital. Total doses of
sedatives (i.e. midazolam, propofol) and analgesic agents (i.e. morphine) were additional
measured outcomes. Results from the study revealed a reduction in the median duration of
mechanical ventilation for the daily interrupted group (4.9 vs. 7.3 days, p=.004). In
addition, there was a reduction in the median length of stay in the ICU and hospital (6.4
vs. 9.9 days, p=.02 and 13.3 vs. 16.9 days, p=0.19; respectively). The total dose of
midazolam was lesser in the daily interruption group (229.8 vs. 425.5 mg; p=.05). The
study found no difference in regard to the incidence of self-extubation. Kress' study
showed positive clinical outcomes with DI in the medical intensive care unit. However,
many clinicians are concerned with the risk-related complications from DI (i.e.
posttraumatic stress disorder and enhanced catecholamine response leading to cardiac
complications). The study did contain limitations: it was limited to a single center and
only included patients that were admitted to the medical intensive care unit. Thus, it is
not clear if the results can be reproduced in other centers or applied to critically-ill
surgical patients. Additionally, there was no mention of the use of PD-SBTs

Can analgesia first effectively facilitate mechanical ventilation for critically ill
patients?

Strøm T et al evaluated the analgesia first in critically ill patients requiring
mechanical ventilation. This was a randomized controlled trial involving 140 patients who
were assigned in a 1:1 ratio to no sedation with analgesia (analgesia-first) group or
sedation with DI group. The analgesia-first group or intervention arm received analgesics
for pain control and sedation only if the analgesia-first approach failed. The
intervention arm had significantly more days without ventilation (13.8 days ± 11.0 vs.
9.6 ± 10.0; p=0.0191) and shorter ICU days and hospital days. No difference was recorded
in the occurrences of accidental extubations, but delirium was significantly higher in
the analgesia-first group (20% vs. 7%, p=0.04).

Conclusion:

A literature search did not reveal any published studies demonstrating whether trauma
patients should be managed with an AFS approach. This study will evaluate mechanical
ventilation and ICU outcomes associated with the AFS approach to facilitate mechanical
ventilation in critically ill patients. All patients will be managed with
institutional-approved PDS-DSI or AFS protocols in the ICU.

  -  Rationale for the study

A limited number of randomized controlled trials:

Using the terms sedation and analgesia, mechanical ventilation discontinuation/weaning,
critically ill, and trauma adult patients, a literature review was conducted to identify
peer-reviewed articles in MEDLINE (1966-November 2021). Articles reviewed included those
published in the English language, review articles, and trials with an emphasis on
prospective, randomized, double-blind, placebo-controlled clinical trials. Reference
citations were reviewed as an additional resource. The literature search revealed no
studies that included the implementation of an AFS in trauma patients.

Which approach is preferred? There are no published studies demonstrating whether
patients should be on AFS versus PDS-DSI for the management of trauma patients requiring
mechanical ventilation beyond 48 hours.

How will this trial help? - Literature review

The above-mentioned literature review and search revealed no studies that included the
implementation of an AFS versus PDS-DSI in ICUs. In addition, under these circumstances,
it is uncertain if an AFS allowing minimal sedation is as efficacious and safe in
comparison to a PDS-DSI.

  -  Use of trial results

The results of this study are clinically and economically relevant. The clinical data
will provide information on what is the preferred sedation practice during mechanical
ventilation weaning. In addition, the study will support a multi-disciplinary approach to
managing mechanically ventilated patients. The measured outcomes from the study will
generate further research to improve patient outcomes, specifically in mechanically
ventilated patients. The economic implications can be potentially derived from the length
of ICU or hospital stay.

Analgesia First Sedation Strategy for Mechanically Ventilated (MV) Trauma Subjects

Protocol Directed Sedation and Daily Sedation Interruption

Medical Director

Time from initiation of MV weaning to successful extubation

Subjects will be randomized to receive analgesia-first sedation by intermittent doses of
Fentanyl (25 mcg), instead of continuous IV infusions. If the intermittent IVP x4 fails
to achieve the target pain score, an infusion starts at 50 mcg/hr and titration by 25 mcg
q15 minutes. If sedation score is not achieved, propofol infusion starts at 5 mcg/kg/min
to achieve goal RASS of 0 to -2. Subjects will be assessed for a ventilator weaning trial
daily.

Subjects will receive Fentanyl for analgesia and midazolam for sedation management. The
RASS score is used to guide sedation to a goal of 0 to -2 and daily sedation by IV
Midazolam at 1 mg/hr and titrated by 1 mg/hr q60 mins. Midazolam boluses are allowed by 1
mg IVP q5 mins x2 before increasing the infusion rate. Propofol and dexmedetomidine are
permitted under existing institutional sedation protocol. Fentanyl IV starts at 50 mcg/hr
and is titrated by 25 mcg/hr q15 mins to achieve target pain score. Fentanyl bolus of 25
mcg IVP q5 min x2 doses is given before increasing the infusion rate. Daily sedation
interruption (DSI) is performed daily and ventilator weaning trial if they pass.

Analgesia-First Sedation in Trauma Patients

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status