Critical Illness Polyneuropathy- An Important Succinylcholine Contraindication

You are requested to your local short-term rehabilitation center for a 67 year old male with respiratory distress.  You arrive to find a patient in significant respiratory distress and altered mental status.  Per staff, the patient sustained an ischemic stroke ten days ago, which resulted in left-sided hemiparesis and some swallowing difficulties.  He has a past medical history of coronary artery disease and hypertension.  This morning, the patient developed acute respiratory distress and 911 was called.  You are concerned about pneumonia or pulmonary embolism in this bed-bound patient, and at this time it does not appear that he is protecting his airway.  Vitals are notable for BP 98/58, HR 128, sinus tachycardia on the monitor, respirations 40, and pulse oximetry 84% on RA.  You call medical control for delayed sequence intubation orders.  What regimen would you like to request?

After multiple clinical pearls on the topic summarizing the latest evidence, there should be little debate on the induction agent for this hypotensive patient.  Etomidate should be avoided in the hypotensive patient in extremis.  You request ketamine for induction sedation for this patient.

How many of you would choose succinylcholine for this patient?  Probably most of the readers would choose succinylcholine.  As you know, succinylcholine exerts its effects by depolarizing the neuromuscular junction by activating acetylcholine receptors.  The succinylcholine continues to activate the receptors, preventing repolarization, or a resetting, of the neuromuscular junction.  The effect continues until pseudocholinesterase, an enzyme in the body, metabolizes the succinylcholine.  The action of the depolarization does cause a potassium ion flux into the blood, typically no more than 1 mEq/L, even in instances of acute renal failure (e.g., dehydration, diabetic ketoacidosis).¹

Most clinicians can rattle off the typical contraindications to succinylcholine administration, such as renal failure/hemodialysis, crush victims, burn victims, and prolonged immobilization/"found down."  Hopefully, if there is enough time to obtain a history, the question of, “Have you or anyone in your family had any problems with anesthesia in the past?” is being asked to ascertain the possibility of the very dangerous malignant hyperthermia.  If you’re really good, you may know that patients with myopathies, such as muscular dystrophy, may result in an acute rhabdomyolysis syndrome from the sudden muscle contractions of the depolarization process.  This may result in a sudden increase in serum potassium.  In fact, there is a black box warning on succinylcholine for this phenomenon, particularly in the pediatric population in which the myopathy may not yet be diagnosed in the patient.²

Much less known, though, is the critical illness polyneuropathy (CIP).  This clinical entity is seen primarily in ICU patients and patients with acute denervating injuries, such as a spinal cord injury or cerebrovascular accident.  In response to the sudden lack of nerve impulses coming from the upper motor neurons (i.e., the brain or spinal cord), the body starts to upregulate, or increase, the number of acetylcholine receptors at the neuromuscular junction in an attempt to make them more sensitive to any nerve signals coming their way.  While the body is unable to activate these neuromuscular junctions due to a functional blockade (e.g., severed spinal cord, ischemic area of brain), succinylcholine can still activate these junctions.  Since there are many more receptors, the activation of them will result in a greater flux of potassium out of the cells.  Potassium increases of 5-15 mEq/L have been seen in these instances, which can certainly cause cardiac arrest.  Because there is a delay in the production of additional receptors, the first 24 hours after an acute neurologic injury is typically safe for succinylcholine, so this should not change your practice with acute strokes.  The risk peaks 5 to 15 days after the denervating injury, and it is believed to last for 2-6 months afterwards.  However, some clinicians believe any patient with a history of denervating injury to be at risk for life-threatening hyperkalemia after succinylcholine.^1,3–5

If you didn’t know this, you’re not alone.  After some clinicians in the UK had two hyperkalemic cardiac arrests in patients like this in their ICU after using succinylcholine, they surveyed other physicians who would be familiar with emergent intubations.  They found that 68.7% of survey respondents chose succinylcholine for intubation.⁶

To summarize, true contraindications to succinylcholine remain renal failure (particularly on hemodialysis), burns (cardiac arrests have occurred with as little as 8% body surface area involved), crush injuries, prolonged immobilization (e.g., found down at home and concern for rhabdomyolysis), myopathies, history of malignant hyperthermia, and, now, recent history of acute denervating injury, such as CVA or spinal cord injury.¹

Case resolution:  You intubate the patient using ketamine and rocuronium, and you administer fentanyl and ketamine for post-intubation sedation.  The patient’s vital signs improve mildly.  At the emergency department, he is found to have a large saddle pulmonary embolus on CT angiography.  He goes to interventional radiology for thrombectomy (removal of the clot), as he cannot receive tissue plasminogen activator (tPA) due to the recent ischemic stroke.  His cardiodynamics improve significantly and he is extubated on hospital day #3.  He returns to rehab, albeit on a different regimen of anticoagulation.

References

1. Stollings JL, Diedrich DA, Oyen LJ, Brown DR. Rapid-sequence intubation: a review of the process and considerations when choosing medications. Ann. Pharmacother. 2014;48(1):62-76. doi:10.1177/1060028013510488.

2. Sandoz Inc. ANECTINE- succinylcholine chloride injection, solution (package insert). 2012. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=579ff759-3099-45f5-befe-c4b79106c87e. Accessed September 21, 2014.

3. Biccard BM, Grant IS, Wright DJ, Nimmo SR, Hughes M. Suxamethonium and critical illness polyneuropathy. Anaesth. Intensive Care 1998;26(5):590-591.

4. Mallon WK, Keim SM, Shoenberger JM, Walls RM. Rocuronium vs. succinylcholine in the emergency department: a critical appraisal. J. Emerg. Med. 2009;37(2):183-8. doi:10.1016/j.jemermed.2008.07.021.

5. Booij LH. Is succinylcholine appropriate or obsolete in the intensive care unit? Crit. Care 2001;5(5):245-6.

6. Hughes M, Grant IS, Biccard B, Nimmo G. Suxamethonium and critical illness polyneuropathy. Anaesth. Intensive Care 1999;27(6):636-638.