Abstract

Intracranial and Hemodynamic Changes after Succinylcholine Administration in Cats. By Cottrell JE, Hartung J, Giffin JP, and Shwiry B. Anesthesia & Analgesia 1983; 62:1006–9. Reprinted with permission.

Bolus injections of succinylcholine (1.5 mg/kg) significantly increased intracranial pressure (ICP) in cats under normal conditions from control levels of 8 +/- 1 mmHg to 16 +/- 3 mmHg (+/- SEM, P less than 0.01), and in the presence of artificially increased ICP from control levels of 27 +/- 1 mmHg to 47 +/- 4 mmHg (P less than 0.01). These approximately 100% increases in ICP were accompanied by a transitory decrease in mean arterial pressure (approximately 10 s), followed by a 15 to 20% increase (P less than 0.05). Pulmonary arterial pressure increased 20 to 30% (P less than 0.05). These results, when considered in conjunction with results previously obtained in humans, suggest that succinylcholine may be contraindicated in neurosurgical patients.

AS residents, most of us are intimidated by the mountain of knowledge that we need to climb. As fellows, falsely confident that we have scaled at least halfway to the peak, an impish notion begins to insinuate itself—the possibility that we might be able to make the mountain a little higher. That was a stimulating aspiration for anyone lucky enough to work with the likes of Ephraim S. [Rick] Siker, M.D. (deceased, previously of University of Pittsburgh Medical Center Mercy Hospital, Pittsburgh, Pennsylvania), and Bernard [Bernie] Wolfson, M.D. (retired, previously of University of Pittsburgh Medical Center Mercy Hospital, Pittsburgh, Pennsylvania), in the early 1970s.

James E. Cottrell, M.D.

James E. Cottrell, M.D.

Our first article tested the hypothesis that preoperative intermittent positive pressure breathing therapy would improve postoperative pulmonary function in patients with chronic obstructive lung disease.1  We were not able to reject the null hypothesis, but according to the custom of Anesthesia & Analgesia in 1973, as first author, I got my picture in the article (fig. 1)—and yes, I sent a reprint to my mother!

Fig. 1.

From Cottrell JE, Siker ES: Preoperative intermittent positive pressure breathing therapy in patients with chronic obstructive lung disease: Effect on postoperative pulmonary complications. Anesth Analg 1973; 52:258–62. Reprinted with permission from Cottrell and Siker.1 

Fig. 1.

From Cottrell JE, Siker ES: Preoperative intermittent positive pressure breathing therapy in patients with chronic obstructive lung disease: Effect on postoperative pulmonary complications. Anesth Analg 1973; 52:258–62. Reprinted with permission from Cottrell and Siker.1 

We had better luck with the null hypothesis in our 1976 paper on airway resistance during sedation of my fellow residents!2  So I got off to a lucky start with pulmonary studies before being drafted by the U.S. Navy, where my lucky streak continued. I was packed for Vietnam when a last-minute change of deployment landed me in the Naval Health Facility at Keflavik, Iceland, and I applied for a faculty appointment at Borgaspitalin in Reykjavik, Iceland, where I did some clinical work and taught medical students, residents, and anesthesia nurses.

After a year in Iceland, I was assigned to coordinate the neuroanesthesia section of the Philadelphia Naval Hospital, Philadelphia, Pennsylvania, which served as sufficient experience to land essentially the same job back in civilian life, as an assistant professor at New York University, New York, New York. As a level 1 trauma center, Bellevue Hospital, New York, New York, had an amazing team of neurosurgeons, neurologists, and vascular neuroradiologists, and a sophisticated brain and spinal cord monitoring facility. But I had mixed feelings. On one hand, with so many experts and so much high-end monitoring, I felt like a kid in a candy store; on the other hand, at times I felt like a first-year resident—if not a first-year medical student!

One of those amazing surgeons was always asking us about intracranial pressure (ICP) and commenting on brain swelling during open cranium procedures. After closure, he would leave a ventricular drain or place a Becker Bolt so we could directly monitor ICP in the neurointensive care unit. Meanwhile, our vascular surgeon loved to use vasoactive drugs to demonstrate how he could relax spastic vessels around an aneurysm with topical papaverine and an intravenous infusion of aminophylline. So, the time was right to formally investigate the effect of commonly used drugs on ICP and cerebral perfusion pressure.

Our first investigation measured changes in ICP, osmolality, and electrolytes after administration of mannitol and furosemide in craniotomy patients. The data warranted our recommendation “that furosemide be used instead of mannitol when diuresis is desired in patients with increased ICP, and in those who have pre-existing cardiac and electrolyte abnormalities.”3,4  Over the ensuing decades, we investigated these and other variables, in vitro and in vivo, after administration of nitroprusside,5,6  nitrous oxide,7  nitroglycerin,8  naloxone,9  succinylcholine,10  nifedipine,11  midazolam,12  thiopental,13  tetrodotoxin,14  diltiazem,15  atracurium,16  trimethaphan,17  lidocaine,18  sevoflurane,19  desflurane,20  and protein kinase Mzeta,21  among others.

From the above list, I chose the publication “Intracranial and Hemodynamic Changes after Succinylcholine Administration in Cats”10  to serve as a Classic Paper Revisited—an article that addressed the concern that a commonly used muscle relaxant could cause ischemic damage from decreased cerebral perfusion pressure when given to a patient with low intracranial compliance, or even irreparable damage from brainstem herniation through the foramen magnum consequent to a large, sudden increase in ICP.

The backstory on our succinylcholine investigation is that we were in the laboratory to determine whether we could measure ICP in cats via cisterna magna puncture with a double-lumen 18-gauge needle in preparation for testing the effect of nifidepine-induced hypotension on normal and elevated ICP. We were pleased to find that our double-lumen technique gave a breath-to-breath sensitive measure of ICP through one lumen with that sensitivity maintained while increasing ICP through the other lumen. We were about to inject a final test dose of nifedipine when pancuronium-induced paralysis appeared to be wearing off. We decided to give an injection of succinylcholine to buy the small amount of time needed give one last dose of nifedipine. To our surprise, the ICP tracing spiked immediately upon injection of succinylcholine (fig. 2). After establishing this effect of succinylcholine with repeated injections, we decided to delay the nifedipine study11  and design a protocol for testing the effect of succinylcholine on ICP.10 

Fig. 2.

Tracing of intracranial pressure (ICP), blood pressure (BP), and pulmonary arterial pressure (PAP) for approximately 100 s. Vertical line, injection of succinylcholine (Sch; 1.5 mg/kg; from cat No. 10, initial ICP increased). Reprinted with permission from Cottrell et al.10 

Fig. 2.

Tracing of intracranial pressure (ICP), blood pressure (BP), and pulmonary arterial pressure (PAP) for approximately 100 s. Vertical line, injection of succinylcholine (Sch; 1.5 mg/kg; from cat No. 10, initial ICP increased). Reprinted with permission from Cottrell et al.10 

Subsequent to our finding in cats, Lanier et al.22,23  found convincing evidence that succinylcholine induces sufficient muscle afferent activity to generate immediate electroencephalographic arousal accompanied by rapidly elevated cerebral blood flow and increased ICP in dogs. To date, seven investigations have found that succinylcholine increases ICP in patients,24–30  suggesting that our observations in cats warranted clinical concern. Two of those investigations also found that succinylcholine-induced increases in ICP can be ameliorated by previous administration of alternative muscle relaxants.29,30 

Although reports relating succinylcholine administration to brain herniation have not been published, absence of evidence is not evidence of absence,31  especially when dealing with rare and life-threatening events.32  Brain herniation aside, empirical evidence supporting the physiologic basis for succinylcholine-induced cerebral ischemia has recently been published in a thoughtfully designed and analyzed retrospective study entitled “Succinylcholine Is Associated with Increased Mortality When Used for Rapid Sequence Intubation of Severely Brain Injured Patients in the Emergency Department.”33 

Competing Interests

The author declares no competing interests.

References

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