Q/A with Tony Friedman Volume 3.0 - RSICP

Rapid Sequence intubation and elevation of ICP

THE QUESTION:

I've noticed that we go to great lengths to premedicate brain bleed/trauma patients before intubation, with the goal of preventing increased intracranial pressure and potential herniation. On the other hand, I've seen intubation delayed up to 10 minutes to get all those medications lined up and administered, and it frequently seems to disrupt the flow of the resuscitation. Are we really doing more good than harm with this?



THE ANSWER:

The elevated ICP with intubation phenomenon has been noted predominantly in patients undergoing intubation for elective neurosurgical procedures who already have ICP monitors in place [1,2]. Obviously, it would be impossible to achieve a similar level of monitoring before RSI in acutely brain-injured patients. The head injury cocktail we're trained to use here consists of lidocaine 1.5 mg/kg, vecuronium 1 mg, fentanyl 3-5 mcg/kg, etomidate .03 mg/kg, and succinylcholine 1.5-2 mg/kg. The first three agents are included to blunt the presumed increase in ICP. I'll present the supporting data for each agent individually.


Lidocaine


Lidocaine is commonly used as a premedicating agent in academic emergency departments in the USA [3] and is used infrequently in the UK [4]. The literature was nicely reviewed in 2001 by an English group and only 6 studies were found, none of which addressed the central issue of whether pretreatment with lidocaine improved the outcome of brain-injured patients undergoing RSI [5]. The strongest supporting evidence for lidocaine comes from a 1980 study by Bedford et al. in which 10 patients undergoing elective resection of cerebral neoplasm received lidocaine prior to intubation, and 10 did not [6]. Other premedications such as morphine, atropine, and diazepam were used in all cases. The authors found that pretreatment with 1.5 mg/kg lidocaine reduced the average rise in ICP with intubation by 12 mmHg. The study's applicability is limited by the small numbers and non-RSI protocol.
Three small studies examined the effect of lidocaine on the ICP response to endotracheal suctioning in intubated patients [7,8,9]. All found that lidocaine reduced either the baseline ICP or the ICP increase with suctioning, but each study was limited by factors such as lack of blinding or small size. Due to the fact that these were non-paralyzed intubated patients undergoing suction rather than laryngoscopy and intubation, the application of these studies to brain-injured patients undergoing RSI is dubious. The other two studies described in the English review provided minimal applicable evidence for lidocaine.
The conclusion of the English reviewers was that the evidence does not support the use of lidocaine for RSI in patients with head injury. However, Ron Walls reviewed essentially the same data in 1993 and found the evidence for using lidocaine "compelling" [10]. I was unable to find more recent literature that addressed the usefulness of lidocaine in RSI. However, it should be noted that the standardized emergency airway course in the United States recommends use of lidocaine in RSI of brain-injured patients. Despite the weakness of supportive evidence, an American physician choosing not to use lidocaine could be vulnerable to accusations of not adhering to the established standard of care.


Vecuronium


The concept of administering a low "defasciculating" dose of a nondepolarizing paralytic agent arises from the observation that succinylcholine itself may contribute to elevation in ICP [1,11]. It should be noted that the evidence of this effect is far from conclusive, and several studies have also been published which reach the opposite conclusion. The mechanism of this purported succinylcholine effect has not been clearly established, but may involve afferent input to the brain from muscle spindle receptors [12].
In a small study of patients administered succinylcholine before and after vecuronium 0.14 mg/kg, significant elevation in ICP was frequently observed with the succinylcholine dose given before vecuronium but not with the dose given after vecuronium [13]. In a small control group receiving two doses of succinylcholine without vecuronium, a small average elevation in ICP was seen with both doses. It should be noted that the groups are very small, the data presentation is significantly flawed, and a full paralyzing dose of vecuronium was used. Interestingly, despite the use of the term "defasciculating dose", patients that were observed to fasciculate with the initial dose of succinylcholine did not sustain significant increase in ICP. Therefore, prevention of fasciculation is unlikely to be a factor in the effect of vecuronium on ICP.
A subsequent study evaluated the effect of pretreatment with a small, non-paralyzing dose of metocurine on the ICP increase with succinylcholine administration [14]. They found an average increase in ICP of 12 mmHg without pretreatment, compared to no significant change in ICP with pretreatment. Only 6 patients were included in each group although they reported that their results achieved significance. They did not offer a pharmacologic explanation of why this particular low dose of a nondepolarizing paralytic would attentuate the ICP response without inducing paralysis. The groups were too small to determine a significant difference in the incidence of fasciculations.
Based primarily on this data, Ron Walls advocates administration of vecuronium or pancuronium at 0.01 mg/kg 2-3 minutes before administration of succinylcholine [10]. Interestingly, an English group reviewed essentially the same data and concluded that there was no significant evidence either that succinylcholine caused elevated ICP in patients with acute brain injury, or that treatment with a low dose nondepolarizing paralytic would attenuate that effect [15]. Ron Walls is listed as a coauthor on that study so he appears to be covering his bases fairly well (note to would-be department chairmen). An alternative would be to use a full dose of nondepolarizing agent as an alternative to succinylcholine, but vecuronium and pancuronium are impractical for RSI due to their delayed onset (approximately 100 seconds) and prolonged effect (approximately two hours). Rocuronium has been advocated but represents a significant additional expense and may not provide optimal conditions for RSI [16].


Fentanyl


The advocacy for use of fentanyl as a premedication in RSI is based on its well-described effects on hemodynamic parameters during intubation. I did not find any studies that addressed the direct effect of fentanyl on ICP. RSI is well described to result in elevations in heart rate, blood pressure, and plasma catecholamine concentrations [17], and this is hypothesized to contribute indirectly to elevated ICP. Fentanyl effectively attenuates these hemodynamic responses [18,19] without inducing significant hypotension [20]. In his review, Ron Walls advocates that it be administered at 3-5 mcg/kg 1-3 minutes before laryngoscopy [10]. This seems to be purely based on the avoidance of tachycardia and hypertension with intubation, and not on any evidence of a direct effect on ICP.
Other agents
There is evidence that thiopental, propofol, and beta blockers attenuate the hemodynamic and intracerebral response to laryngoscopy and intubation, but their hypotensive qualities have made their use unpopular in brain-injured patients. In very hypertensive patients (e.g spontaneous ICH) thiopental especially may be considered as an induction agent at 3-5 mg/kg [21].
It is important to remember that virtually all data supporting the use of premedication in brain injury is based on ICP measurements in elective neurosurgical patients who underwent conventional induction of anesthesia rather than RSI. Therefore, it is difficult to advocate their use prior to RSI in acutely brain-injured patients. However, none of these medications has been demonstrated to have any harmful effects when used during RSI. I think that the decision to use these medications can be made by the individual on a case by case basis, keeping in mind that the top priority should always be securing the airway and maintaining adequate oxygenation. I don't think the evidence justifies delaying intubation in a hypoxic patient, as hypoxia has been definitively associated with increased mortality in traumatic brain injury [22].
Considering the controversy that has existed for 10-15 years regarding premedication, it is rather surprising that no randomized prospective trial of these agents has been published that addresses neurologic outcome and mortality. It seems that such a study would be relatively simple to design and implement, considering the fairly high frequency of brain-injured patients requiring intubation, and could result in a significant paradigm shift in emergency medicine practice either here or on the other side of the Atlantic.

References:
1. Burney et al. 1975 Anaesth Analg 54:687
2. Rudy et al. 1986 Heart Lung 15:488
3. Silber et al. 1997 Am J Emerg Med 15:263
4. Butler et al. 2001 Emerg Med J 18:343
5. Robinson et al. 2001 Emerg Med J 18:453
6. Bedford et al. in Shulman et al. 1980 Intracranial Pressure IV, Springer: 595
7. Donegan et al. 1980 Anesthesiology 52:516
8. White et al. 1982 Anesthesiology 57:242
9. Yano et al. 1986 Anesthesiology 69:651
10. Walls. 1993 Ann Emerg Med 22:1008
11. Thompson et al. 1982 Ann Emerg Med 10:526
12. Mori et al. 1973 Br J Anaesth 45:605
13. Minton et al. 1986 Anesthesiology 65:165
14. Stirt et al. 1987 Anesthesiology 67:50
15. Clancy et al. 2001 Emerg Med J 18:373
16. Perry et al. 2003 Cochrane Database Syst Rev Issue 1
17. Takeshima et al. (1964) Anaesth Analg 43:201
18. Ebert et al. (1989) Can J Anaesth 36:301
19. Helfman et al. (1991) Anesth Analg 72:482
20. Miller et al. (1988) Can J Anaesth 35:219
21. Shapiro et al. (1973) Br J Anaesth 45:1057
22. Stocchetti et al. 1996 J Trauma 40:764