Clinical Pearl 71: Fentanyl for ICP/CPP

You have 54 y/o male in an MVC who is is found with GCS of 5, with extensor posturing and obvious head trauma.  Concerned for traumatic brain injury, the paramedics at the scene performed successful rapid sequence intubation using fentanyl, ketamine and succinylcholine.  The patient was transported to a trauma center. A CT scan of the brain revealed multiple parenchymal hemorrhages. The medical director at the local hospital called to question the use of fentanyl in the setting of traumatic brain injury and the possibility of hypotension. Does Fentanyl during the perintubation period effect cerebral perfusion pressure (CPP)??

Larygnoscopy and tracheal intubation cause hypertension and tachycardia, which may lead to increases in intracranial pressure, a problem of serious consequence in vulnerable patients. Of special interest here are the acute head trauma patients who undergo rapid sequence intubation, and for who changes in cerebral perfusion pressure may have deleterious effects [1, 2]. Various drugs such as fentanyl have been used to modify these changes in hemodynamics, including lidocaine, beta-blockers and fentanyl and have been studied extensively [3].  A prospective, randomized, double-blinded study of healthy ASA I & II patients undergoing elective intubation with appropriate NPO status evaluated the efficacy of esmolol (1.5mg/kg), fentanyl (1mcg/kd) and lidocaine (1.5mg/kg) in blunting the catecholamine response of laryngoscopy as measured by heart rate, mean arterial blood pressure, and a derived rate-pressure product. In this study of 120 patients, esmolol was shown, with statistical significance to be superior to both fentanyl and lidocaine[4]. This study is interesting but somewhat limited in the emergency setting where patients are rarely NPO, healthy, with a low-grade ASA status, and stable enough to tolerate the 2-3 minutes of pre-medication utilized in the study protocol.

The use of opioids for rapid sequence intubation in trauma has been extensively reviewed in the literature. In 2014, Pouraghaei et al evaluated 90 patients who required emergent intubation following trauma. Patients were randomized into three different groups, those receiving alftentanil (20microgm/kg), fentanyl (2microgm/kg) and sufentanil (0.2microgm/kg), respectively [5]. Vital signs such as heart rate, blood pressure, oxygen saturation and end-tidal carbon dioxide were measured 5 minutes before and 3, 5 and 10 minutes after intubation. No statistically significant differences were observed in the hemodynamic parameters (systolic and diastolic blood pressure, heart rate, oxygen saturation and end tidal carbon dioxide) during intubation and up to ten minutes after successful endotracheal intubation. While small in sample size, this study did further support the use of fentanyl as a safe sedating agent during RSI. 

In the SHRED study (1998), the authors sought to compared thiopental, fentanyl, and midazolam for rapid-sequence induction intubation [6].  In this double-blinded study, 86 patients undergoing RSI in the emergency department were randomly selected to receive thiopental (5 mg/kg), fentanyl (5 microg/kg), or midazolam (0.1 mg/kg) before paralysis was induced. Outcome measures were mortality, speed and ease of intubation, and hemodynamic changes. In all three groups, patients exposed to multiple attempts at intubation manifested pronounced hypertension. Fentanyl proved to have the most neutral hemodynamic profile during RSI, with  minimal changes in heart rate, systolic and diastolic blood pressure when administered in the peri-intubation period.

In his 1993 review in Annals of Emergency Medicine, Wall described the role of opioids in the performance of rapid sequence intubation in the patient with acute traumatic brain injuries [7]. Wall cite’s that the use of fentanyl is advantageous in that it is readily available in most emergency departments, has a rapid rate of onset and has favorable cardiovascular effects. Fentanyl may be administered 3-5microgrms/kg about one to three minutes before laryngoscopy and intubation. Larger doses of fentanyl may lead to hypoventilation thus leading to hypercarbia in the spontaneously breathing patient. If a patient is hypotensive, fentanyl should be highly considered due to its proven stable hemodynamic profile.

Despite it’s excellent sedating quality and favorable hemodynamic profile, questions remain about the actual effect of fentanyl on ICP. While some studies have suggested that the administration of opioids in bolus dosing results in transient increases in ICP, the clinical ramifications of such transient rises is unclear.  One proposed mechanism for this subtle rise in the ICP has been that a drop in MAP results in the initiation of autoregulatory processes in the brain meant to preserve brain function which, lead to vasodilation in the cerebral vasculature [8].

So? The end-game is that Fentanyl is likely safe to use in patients was suspected rises in ICP, and may in fact be beneficial in the peri-intubation phase to reduce the risk for increased ICP associated with direct laryngoscopy. 

Bibliography

1. Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation. Schribman AJ, Smith G, Achola KJ. British Journal of Anaesthesia. 1987;59:295-9.
2. Neurocirculatory responses to intubation with either an endotracheal tube or laryngeal mask airway in humans. Akbar AN, Muzi M, Lopatka CW, Ebert TJ. Journal of Anesthesia 1996;8:194-7
3. Use of lidocaine and fentanyl premedication for neuroprotective rapid sequence intubation in the emergency department. Kuzak N, Harrison DW, Zed PJ - CJEM - March 1, 2006; 8 (2); 80-4
4.  Effects of Esmolol, Lidocaine and Fentanyl on Haemodyamic Responses to Endotracheal Intubation: A Comparative Study. Bakiye U, Mustafa O, Erdal G, Osman NA, Feray G. Clinical Drug Investigation. 2007;27 (4): 269-277
5. Comparison between the effects of alfentanil, fentanyl and sufentanil on hemodynamic indices during rapid sequence intubation in the emergency department. Pouraghaei M, Moharamzadeh P, Soleimanpour H, Rahmani F, Safari S, Mahmoodpoor A, Ebrahimi Bakhtavar H, Mehdizadeh Esfanjani R - Anesth Pain Med - February 1, 2014; 4 (1); e14618
6. Randomized, double-blind study on sedatives and hemodynamics during rapid-sequence intubation in the emergency department: The SHRED Study. Sivilotti ML, Ducharme J - Ann Emerg Med - March 1, 1998; 31 (3); 313-24
7. Rapid Sequence Intubation in Head Trauma. Walls, R. Ann Emerg Med – June 1993. Accessed online September 2016.
   
8. Effects of Fentanyl on Intracranial Pressure and Cerebral Perfusion Pressure during Hypocapnia Moss E, Powell D.  Clinicalkey.com – September 15; 50, 779 Br. F Anaesth (1978) Macmillan Journals. 1978