CARDIAC ARREST DURING A PEDIATRIC TONSILLECTOMY

Physician anesthesiologist at Stanford at Associated Anesthesiologists Medical Group
Richard Novak, MD is a Stanford physician board certified in anesthesiology and internal medicine.Dr. Novak is an Adjunct Clinical Professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University, the Medical Director at Waverley Surgery Center in Palo Alto, California, and a member of the Associated Anesthesiologists Medical Group in Palo Alto, California.
emailrjnov@yahoo.com
THE ANESTHESIA CONSULTANT

A 12-year-old boy and his mother walk into a surgery center. The child is scheduled for a tonsillectomy, and is otherwise healthy. The anesthesiologist induces general anesthesia, and ten minutes later the patient has ventricular arrhythmias which descend into a cardiac arrest. Advanced Cardiac Life Support (ACLS) measures are applied, but the child cannot be resuscitated, and is declared dead. What caused this cardiac arrest during a pediatric tonsillectomy?

This is an actual closed malpractice case which I was asked to review. The anesthesiologist induced general anesthesia with propofol and a paralytic drug called succinylcholine (sux-in-ol-KOH-leen), and then inserted a breathing tube successfully into the patient’s windpipe. All vital signs were normal. Sevoflurane, nitrous oxide, and 50% oxygen were ventilated into the patient’s lungs. The surgeon began the tonsillectomy. One minute later the cardiac arrest occurred. The anesthesiologist followed ACLS guidelines, but standard ACLS treatments and hyperkalemia (elevated potassium concentration) treatments were unsuccessful.

Succinylcholine is an intravenous muscle relaxant (paralytic) drug commonly used in the United States. Succinylcholine is an old drug—available since 1951—which has the distinction of being the most rapid-acting intravenous muscle relaxant, and also the shortest-acting muscle relaxant. Succinylcholine is an important drug in an anesthesiologist’s toolkit. When an airway emergency threatens a patient’s life, such as the unexpected occurrence of laryngospasm, succinylcholine is the emergency drug of choice to paralyze the patient, relax the spasm of the vocal cords, and enable the anesthesiologist/emergency room physician/acute care physician to insert a life-saving breathing tube into the trachea.

But succinylcholine can be a dangerous drug. The Food and Drug Administration (FDA) placed a Black Box Warning on succinylcholine in 1994. The current succinylcholine warning in the PDR (Prescribers’ Digital Reference) reads:

Succinylcholine is contraindicated in patients with a personal or familial history of malignant hyperthermia and/or skeletal muscle myopathy. Malignant hyperthermia may be precipitated by succinylcholine; concomitant use of volatile anesthetics may further increase this risk. 

In neonates, infants, children, and adolescents, reserve the use of succinylcholine for emergency intubation or instances where immediate securing of the airway is necessary (e.g., laryngospasm, difficult airway, full stomach, or lack of intravenous access). 

There have been rare reports of ventricular dysrhythmias and fatal cardiac arrest secondary to rhabdomyolysis with hyperkalemia, primarily in healthy-appearing pediatric patients who were subsequently found to have undiagnosed skeletal muscle myopathy, most frequently Duchenne’s muscular dystrophy. 

Affected pediatric patients are typically, but not exclusively, males 8 years or younger. Although some patients have no identifiable risk factors, a careful history and physical exam may identify developmental delays suggestive of myopathy, and a preoperative creatinine kinase could identify patients at risk. 

Closely monitor body temperature, expired CO2, heart rate, blood pressure, and electrocardiogram in pediatric patients to help detect early signs of malignant hyperthermia and/or hyperkalemia. 

The rhabdomyolysis syndrome often presents as peaked T-waves and sudden cardiac arrest within minutes of succinylcholine administration. If cardiac arrest occurs immediately after succinylcholine administration, institute treatment for hyperkalemia (e.g., intravenous calcium, bicarbonate, glucose with insulin, hyperventilation). If malignant hyperthermia is suspectedinitiate appropriate treatment (e.g., dantrolene, supportive care) concurrently.”

Per the Black Box warning, succinylcholine has the potential for inducing life threatening hyperkalemia in children with undiagnosed skeletal muscular dystrophies. Severe hyperkalemia and ventricular arrhythmias followed by cardiac arrest may occur in apparently healthy children who have an occult muscular dystrophy (usually Duchenne’s muscular dystrophy). An occult muscular dystrophy is a rare inherited disease. The global prevalence of Duchenne’s muscular dystrophy is 7.1 cases per 100,000 males, and 2.8 cases per 100,000 in the general population. The Black Box warning on succinylcholine recommends to “reserve use in children for emergency intubation or need to immediately secure the airway.”

The Black Box warning applies to neonates, infants, children and adolescents. No parent wants their son or daughter under the age of 18 to electively receive a drug which has an FDA Black Box Warning for use in adolescents. No parent wants their neonate, infant, child, or adolescent to have a risk of sudden cardiac arrest under general anesthesia for a common elective surgery.

In 1994 the Anesthesia Patient Safety Foundation (APSF) published a sentinel article about the risks of succinylcholine in pediatric anesthesia. The article reviews the history of the succinylcholine warning: “In 1992, Drs. H. Rosenberg and G. Gronert published a letter in Anesthesiology briefly reviewing four deaths in male children under the age of eight who had received halothane and then succinylcholine. These cases were identified through the Malignant Hyperthermia (MH) Hotline. Reference was also made to ‘11 similar cases’ identified through the German MH Hotline. Their letter concluded with the statement: ‘We have notified the Food and Drug Administration of this potential problem and recommended that anesthesiologists carefully consider the indications for use of succinylcholine in young children.’ This letter was accepted for publication August 24,1992.” The article goes on to emphasize “the need for prompt and appropriate treatment should hyperkalemic arrest occur. This treatment involves the intravenous administration of calcium. With proper treatment, approximately 50% of patients have survived this catastrophic hyperkalemia.” The Black Box warning specifically states, “If cardiac arrest occurs immediately after succinylcholine administration, institute treatment for hyperkalemia (e.g., intravenous calcium, bicarbonate, glucose with insulin, hyperventilation).”

Despite the Black Box warning, how often is succinylcholine still used for non-emergency pediatric anesthetics in the United States? No one knows. I can attest that during a recent Quality Assurance review in the Northern California, I saw anesthetic records from a board-certified anesthesiologist who administered succinylcholine to a 14-year-old boy for elective ear surgery. I discussed this with the anesthesiologist, who was unaware they were doing anything dangerous.

There is an excellent alternative to the elective use of succinylcholine. For most cases, pediatric or adult, the muscle relaxant rocuronium is a superior alternative to succinylcholine. Succinylcholine is the IV muscle relaxant with the most rapid onset, but large doses (0.9 mg/kg) of rocuronium are nearly as rapid as succinylcholine, without any of succinylcholine’s risks.   Succinylcholine is also the IV muscle relaxant which wears off the fastest, but since the year 2015 FDA approval of the muscle relaxant reversal drug sugammadex (Bridion), an intubating dose of rocuronium can be rapidly reversed within 3 minutes by administering 16 mg/kg of sugammadex

Succinylcholine remains an important drug for the treatment of airway emergencies. I would never begin a general anesthetic if I did not have a vial of succinylcholine immediately available in case of an airway emergency. In addition, succinylcholine is important because it can be administered intramuscularly (in a patient who has no IV). For example, if a child is undergoing an inhalational induction of general anesthesia with sevoflurane vapor prior to a surgery, and the child suddenly goes into laryngospasm before any IV can be started, (this does occur, not uncommonly, and is a true emergency), the appropriate treatment is an intramuscular injection of 4 mg/kg of succinylcholine. The child will become paralyzed within minutes, and the anesthesiologist can then insert a life-saving breathing tube. (The mean onset of paralysis with 4 mg/kg intramuscular succinylcholine in children ages 1 to 10 ranges from 2.9 to 3.9 minutes.)

I’ve written about the advantages and risks of succinylcholine previously in the article, “Succinylcholine: Vital Drug or Obsolete Dinosaur?”  

I also refer you to the published article, “Is There Still a Role for Succinylcholine in Contemporary Clinical Practice?

The take home messages from this case study of a cardiac arrest during a pediatric tonsillectomy are:

  • If you’re an anesthesia provider, do not administer succinylcholine to a neonate, infant, child, or adolescent for an elective surgery. The Black Box warning on succinylcholine recommends to “reserve use in children for emergency intubation or need to immediately secure the airway.”
  • If you’re a parent, prior to your son or daughter’s surgery, be empowered to ask your child’s anesthesiologist if they’re aware of the Black Box warning on succinylcholine. 
  • Nobody wants a death brought on by an elective anesthetic.

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SUCCINYLCHOLINE: VITAL DRUG OR OBSOLETE DINOSAUR?

Physician anesthesiologist at Stanford at Associated Anesthesiologists Medical Group
Richard Novak, MD is a Stanford physician board certified in anesthesiology and internal medicine.Dr. Novak is an Adjunct Clinical Professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University, the Medical Director at Waverley Surgery Center in Palo Alto, California, and a member of the Associated Anesthesiologists Medical Group in Palo Alto, California.
emailrjnov@yahoo.com
THE ANESTHESIA CONSULTANT

Succinylcholine: vital drug or dinosaur? Succinylcholine (sux) has the wonderful advantage of rendering a patient paralyzed in less than a minute, and the discouraging disadvantage of a long list of side effects that make the drug problematic.

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A vial of succinylcholine

I would never begin an anesthetic without succinylcholine being immediately available. No other muscle relaxant supplies as rapid an onset of action and as short a duration of action. An intravenous dose of 1 mg/kg of succinylcholine brings complete paralysis of the neuromuscular junction at 60 seconds, and recovery to 90% of muscle strength in 9 – 13 minutes. (Miller’s Anesthesia, 7th Edition, 2009, Chapter 29, Pharmacology of Muscle Relaxants and Their Antagonists). If a patient has an acute airway disaster on induction such as laryngospasm or pulmonary aspiration, no drug enables emergency endotracheal intubation as quickly as succinylcholine. That said, I never use succinylcholine unless I have to. The drug has too many side effects and rocuronium is often a better choice. For an elective anesthetic on a patient who has fasted and has an empty stomach, one almost never needs to use succinylcholine. If you do use sux, you are exposing your patient to the following side effects:

1. Myalgias. Your patient complains to you the following day, “Doc, I feel like I was run over by a truck.” Because the majority of anesthetics are currently done on outpatients, and because you do not personally interview these patients the following day, you won’t be aware of the degree of muscle pain you’ve induced by using the depolarizing relaxant succinylcholine. Published data quantitates the incidence of post-succinylcholine myalgia as varying from 0.2 % to 89% (Brodsky JB, Anesthesiology 1979; 51:259-61), but my clinical impression is that the number is closer to 89% than it is to 0.2%. Myalgias aren’t life-threatening, but if you ever converse with your patient one day after succinylcholine and they complain of severe muscle aches, you’ll wish you’d chosen another muscle relaxant if possible.
2. Risk of cardiac arrest in children. Succinylcholine carries a black box warning for use in children. Rare hyperkalemia and ventricular arrhythmias followed by cardiac arrest may occur in apparently healthy children who have an occult muscular dystrophy. The black box warning on succinylcholine recommends to “reserve use in children for emergency intubation or need to immediately secure the airway.”
3. Hyperkalemia, with an average increase of 0.5 mEq in potassium concentration after intravenous succinylcholine injection.
4. Cardiac arrest in patients with a history of severe trauma, neurologic disease or burns. There’s a risk of cardiac arrest with succinylcholine use in patients with severe burns, major trauma, stroke, prolonged immobility, multiple sclerosis, or Guillian-Barré syndrome, due to an up-regulation of acetylcholine. The increase in serum potassium normally seen with succinylcholine can be greatly increased in these populations, leading to ventricular arrhythmia and cardiac arrest. There is typically no risk using succinylcholine in the first 24 hours after the acute injury.
5. Cardiac arrhythmias. Both tachy and bradycardias can be seen following the injection of succinylcholine.
6. Increase in intraocular pressure, a hazard when the eye is open or traumatized.
7. Increase in intragastric pressure, a hazard if gastric motility is abnormal or the stomach is full.
8. Increase in intracranial pressure, a hazard with head injuries or intracerebral bleeds or tumors.
9. Malignant Hyperthermia (MH) risk. The incidence of MH is low. A Danish study reported one case per 4500 anesthetics when triggering agents are in use (Ording H, Dan Med Bull, 43:111-125), but succinylcholine is the only injectable drug which is a trigger for MH, and this is a disincentive to use the drug routinely.
10. Prolonged phase II blockade. Patients who have genetically abnormal plasma butyrylcholinesterase activity have the risk of a prolonged phase II succinylcholine block lasting up to six hours instead of the expected 9 – 13 minutes. If you’ve ever had to stay in the operating room or post-anesthesia recovery room for hours with a ventilated patient after their surgery ended because your patient incurred prolonged blockade from succinylcholine, you won’t forget it, and you’ll hope it never happens again.

What does a practicing anesthesiologist use instead of succinylcholine? Rocuronium.

A 0.6 mg/kg intubating dose of the non-depolarizing relaxant rocuronium has an onset time to maximum block of 1.7 minutes and a duration of 36 minutes. The onset time can be shortened by increasing the dose to a 1.2 mg/kg, a dose which has an onset time to maximum block of 0.9 minutes and a duration of 73 minutes. These durations can be shortened by reversing the rocuronium blockade as soon as one twitch is measured with a neuromuscular blockade monitor. Thus by using a larger dose of rocuronium, practitioners can have an onset of acceptable intubation conditions at 0.9 X 60 seconds = 54 seconds, compared to the 30 seconds noted with succinylcholine, without any of the 10 above-listed succinylcholine side effects. The duration of rocuronium when reversed by neostigmine/glycopyrrolate can be as short as 20 – 25 minutes, a time short enough to accommodate most brief surgical procedures.

Now that sugammadex is commercially available, we can reverse rocuronium blockade in seconds, making rocuronium shorter in duration than succinylcholine.

Here is a list of surgical cases once thought to be indications for using succinylcholine, which I would argue are now better served by using a dose of rocuronium followed by early reversal with sugammadex:

1) Brief procedures requiring intubation, such as bronchoscopy or tonsillectomy.
2) Procedures which require intubation plus intraoperative nerve monitoring, such as middle ear surgery.
3) Procedures requiring intubation of obese and morbidly obese patients who appear to have no risk factors for mask ventilation.
4) Procedures requiring full stomach precautions and cricoid pressure, in which the patient’s oxygenation status can tolerate 54 seconds of apnea prior to intubation. This includes emergency surgery and trauma patients. Miller’s Anesthesia (Chapter 72, Anesthesia for Trauma) discusses the induction of anesthesia and endotracheal intubation for emergency patients who are not NPO and may have full stomachs. Either succinylcholine or rocuronium can be used, with succinylcholine having the advantage of a quicker onset and the 1.2 mg/kg of rocuronium having the advantage of lacking the 10 side effects listed above. The fact that succinylcholine takes 9 – 13 minutes to wear off makes it riskier than rocuronium, which can be reversed in seconds by sugammadex. Waiting for 9 minutes for a return to spontaneous respirations after succinycholine would be associated with severe hypoxia.

On the other hand, succinylcholine is the sole recommended muscle relaxant for:

1) Cesarean sections. Miller’s Anesthesia (Chapter 69, Anesthesia for Obstetrics) still recommends thiopental and succinylcholine for Cesarean sections that require general anesthesia, and I would be loath to disagree with our specialty’s Bible.
2) Electroconvulsive therapy (ECT) for depression. Miller’s Anesthesia (Chapter 79, Anesthesia at Remote Locations) recommends partial muscle relaxation during ECT, and recommends small doses of succinylcholine (0.5 mg/kg) to reduce the peripheral manifestations of the seizure and to prevent musculoskeletal trauma to the patient.
3) Urgent intubation or re-intubation in a patient when every second counts, e.g. a patient who is already hypoxic. A subset of this indication is the patient who is being mask-induced and becomes hypoxic and requires intramuscular succinylcholine injection.
4) Laryngospasm either during mask induction or post-extubation, in which the patient requires urgent paralysis to relax the vocal cords.

In conclusion, most indications for muscle relaxation are better handled by using the non-depolarizing drug rocuronium rather than succinylcholine. However, because of the four recommended uses for succinylcholine listed in the previous paragraph, none of us would ever practice anesthesia without a vial of succinylcholine in our drawer for immediate availability.

I try very, very hard to minimize my use of succinylcholine, and so should you. But to answer our original question… succinylcholine is still a vital drug and not a dinosaur at all.

 

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