Rather than continuing to reiterate older practices, is it time to modify "LOAD" pretreatment for RSI? Let's talk "LOAD" -
Rapid sequence intubation (RSI) is the preferred technique to secure an airway in the emergency department. This is done to optimize intubating conditions and prevent the physiologic response (gag reflex) with attempts to pass an endotracheal tube. The Six Ps of RSI include: 1) preparation 2) preoxygentation 3) pretreatment 4) paralysis and induction 5) placement of tube 6) postintubation management.
Pretreatment was originally used with the acronym "LOAD" (lidocaine, opioids, atropine, and defasciculating dosing). These treatments were initially proposed to mitigate the sympathetic response and blunt elevations in intracranial pressures (ICPs) for severe traumatic braininjuries. An increase in catecholamine surge can cause abrupt increase in ICP and edema, resulting in subsequent worsening hemorrhage.
This practice has fallen out of favor given the lack of clinical evidence to support routine use. Rather than continuing to reiterate older practices, is it time to modify "LOAD" pretreatment for RSI? Let's briefly discuss "LOAD" pretreatment and how I've modified the acronym to make it more pertinent/applicable to my practice.
"LOAD" Pretreatment for RSI
Lidocaine
There has been conflicting evidence on lidocaine's neuroprotective properties for pretreatment in severe TBIs.
Acute concerns with lidocaine for RSI is the association of hypotension.
No longer recommended given insufficient evidence to support routine use.
Opioids
Opioids have the most evidence for neuroprotective properties from extensive literature from anesthesia.
Pretreatment fentanyl has been associated with prevention of increases in blood pressure, in addition to preventing release of endorphins and norepinephrine.
Caution with fentanyl-induced hypotension as this may contribute to neurologic injury.
Fentanyl doses used for pretreatment range from 2 to 5 mcg/kg. The lower end of dosing range should be sufficient but limited by patient hemodynamics.
Atropine
Bradycardia is an uncommon, yet serious adverse effect of succinylcholine that occurs more often in pediatrics.
Instances of bradycardia can still occur even with pretreatment atropine.
The 2015 Pediatric Advanced Life Support Guidelines recommend limiting the use of prophylactic atropine for pretreatment.
Not recommended for routine use.
Defasciculation Dosing
The initial thought of using "defasciculation" dosing with a small dose of non-depolarizing neuromuscular blocker prior to succinylcholine to prevent fasciculations. It was believed that fasciculations may contribute to increased ICPs.
It appears that this was an inferred practice from patients undergoing elective surgery with brain tumors.
No trials support the clinical benefit of this practice.
Modified "LOAD Pretreatment"
LOAD: Lidocaine, Opioids, Access, Down or Delayed
My modification of "LOAD" is not necessarily intended to GIVE medications for pretreatment. It includes medications you can give prior to paralyzing the patient, but the thought-process is more tailored towards anticipating complications associated with RSI and step back to ensure you have a plan in case things go south. Ask yourself the following questions for each component.
Lidocaine
Is this an indication for topical or nebulized lidocaine for an awake intubation?
An awake intubation should be considered any time there are concerns for difficult airway management (trauma, obstruction, body habitus, etc.)
Nebulized lidocaine 4% has been shown to provide adequate airway anesthesia and optimal intubating conditions. Preferable.
Topical lidocaine applied to the larynx is another route that may help with airway anesthesia.
Opioids (same as above)
Does the patient need opioids for pain control or neuroprotection?
Opioids have the most evidence for neuroprotective properties from extensive literature from anesthesia.
Pretreatment fentanyl has been associated with prevention of increases in blood pressure, in addition to preventing release of endorphins and norepinephrine.
Caution with fentanyl-induced hypotension as this may contribute to neurologic injury.
Fentanyl doses used for pretreatment range from 2 to 5 mcg/kg. The lower end of dosing range should be sufficient but limited by patient hemodynamics.
Access
What access do I have to get the medications into the patient?
Knowing what medication to give does the patient no good if we cannot get the drug into the patient.
As the pharmacist, you need to know alternatives based on available access.
Is the patient altered and combative? Give ketamine intramuscular to obtain access (can serve as induction if IV access obtained quickly). Does the patient need contrast for imaging? You'll need a separate line for post-intubation sedation continuous infusions. If that isn't in your books, what intermittent strategies do you have to maintain sedation without delaying scans?
You might be the one simply calling for an intraosseous kit.
Down or Delay
Does the patient need agents for vasoactive support or delayed sequence intubation?
Down hemodynamics
Hypotension post-intubation is associated with worse outcomes.
Endotracheal intubation is often an emergent life-saving intervention. Patients may already be hemodynamically unstable.
Procure IV push dose or continuous infusions vasopressors. IV push dose pressors are associated with adverse events secondary to human error. It may preferable to opt for the infusion pending patient acuity.
Delayed sequence intubations (DSI)
DSI is the technique of delayed administration of paralytics if the physician has uncertainty of successfully passing an endotracheal tube given patient conditions (swelling from angioedema, morbidly obese with stout neck, etc).
The physician will either continue towards awake intubation (see above) or delay giving paralytics with a caveat.
Agents for delayed sequence intubation are physician-dependent but the intent is to maintain respiratory drive as emergency clinician rapidly attempts to take a view of the vocal cords.
Ketamine is excellent for this as it preserves respirations and dissociates the patient. With a clear view, the paralytic can be pushed.
It would be preferable to have an agent that is rapid acting and quick offset. Procedural sedation dose of propofol is another alternative, but has limitations.
Modernizing the "LOAD"
The original use of LOAD has fallen out practice for severe TBIs, but yet, the acronym is still discussed/taught as a part of pretreatment. Out of lidocaine, opioids, atropine, and defasciculation dosing, opioids are the only intervention with consistent data on neuroprotective properties in the setting of RSI and TBI. I have modified the acronym "LOAD" to lidocaine, opioids, access, and down or delay. Going through each component allows me to anticipate complications from anticipated airways.
Mark Nguyen, PharmD, BCEMP
References
Kramer et al. Rapid Sequence Intubation in Traumatic Brain-injured Adults. Cureus. 2018 Apr; 10(4): e2530.
Bucher J, Koyfman A. Intubation of the Neurologically Injured Patient. Journal of Emergency Medicine, 2015-12-01, Volume 49, Issue 6, Pages 920-927
Ahmad et al. Difficult Airway Society guidelines for awake tracheal intubation (ATI) in adults. Anaesthesia. 2020 Apr;75(4):509-528. doi: 10.1111/anae.14904.
Rosen's Emergency Medicine : Concepts and Clinical Practice. St. Louis :Mosby, 2022.
James, R.R. (2019) Roberts and Hedges’ Clinical Procedures in Emergency Medicine and Acute Care. 7th Edition, Elsevier, Amsterdam.
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