A Case of Succinylcholine-Induced Hyperkalemia

A Case of Succinylcholine-Induced Hyperkalemia 

(Authored by Dr. Merrill Tarr, Department of Molecular and Integrative Physiology, University of Kansas Medical Center) 

Case History: The following case history relates to a patient who was treated at Saint Luke’s Hospital, Kansas City, Missouri and is condensed from the following paper (Matthews JM. Succinylcholine-Induced Hyperkalemia and Rhabdomyolysis in a Patient with Necrotizing Pancreatitis. Anesth Analg 2000;91:1552–4. 

“A 54-yr-old, 114 kg man presented to the hospital after the abrupt onset of abdominal pain accompanied by severe nausea and vomiting. A presumptive diagnosis of pancreatitis was confirmed by increased amylase and lipase. Abdominal computed tomography showed severe inflammation of the pancreas with probable necrosis. The pancreatitis was attributed to the presence of gallstones.” .... “On the fifth day of admission, respiratory failure necessitated orotracheal intubation and mechanical ventilation. Midazolam infusion provided adequate conditions for ventilatory support, and nondepolarizing muscle relaxants were not administered. Ventilatory support continued for 1 wk before it was successfully terminated and the trachea extubated. On the 35th day of hospitalization, the patient again developed respiratory failure associated with large bilateral pleural effusions. Anesthesia personnel were summoned to the intensive care unit (ICU) to perform an endotracheal intubation. Initial assessment revealed an obese man in obvious respiratory distress. Topical local anesthetic was applied to the oropharynx, and direct laryngoscopy was attempted. This was unsuccessful because of the patient’s confusion and inability to cooperate. Midazolam was titrated IV to a total dose of 8 mg without appreciable sedative effect. Because of the patient’s vigorous resistance to the procedure, his large body habitus with associated broad neck, his tolerance to standard sedatives, and the perceived need for expedient intubation, the decision was made to facilitate laryngoscopy with thiopental and succinylcholine. After breathing oxygen, thiopental 200 mg and succinylcholine 80 mg were given IV as cricoid pressure was applied. Successful endotracheal intubation was accomplished within 60 s, and the oxygen saturation increased to 96%. Approximately 2 min after intubation, the previously normal cardiac rhythm changed to a wide complex bradycardia. A presumptive diagnosis of hyperkalemia was made, and IV calcium chloride was given. The electrocardiographic complexes continued to widen to a sine-wave pattern followed by asystole. Cardiopulmonary resuscitation was performed. Epinephrine, sodium bicarbonate, and insulin/glucose were administered, and a blood sample was obtained to determine serum potassium. After 12 min of cardiopulmonary resuscitation, a narrow complex tachycardia resumed that was associated with good peripheral pulses. Defibrillation was not performed. Initial potassium level obtained during cardiopulmonary resuscitation was 9.8 mEq/L. Approximately 10 min after restoration of cardiac rhythm, the serum potassium had returned to a normal level of 4.1 mEq/L.” The patient died on the 41st day after admission due to rhabdomyolysis-induced kidney failure. 

Questions

1. Wheredidthepotassiumcomefromthatproducedtheincreasedplasma potassium concentration in this patient?
   
2. Inthispatient,bradycardiaoccurredsoonaftertheadministrationof succinylcholine. With regards to SA-node cells, what effect does hyperkalemia have on 1) maximum diastolic potential, 2) rate of phase 4 depolarization, 3) rate of phase 0 depolarization, and 4) rate of phase 3 repolarization? Which of these would contribute to the production of a bradycardia?
   
3. Withregardstoquestion2,bywhatmechanism(s)doeshyperkalemia produce each of the effects on SA-node cells?
   
4. WithregardstotheECG,whateffectsdoeshyperkalemiatohaveon1)PR interval, 2) RT interval, and 3) T-wave?
   
5. Withregardstoquestion4,bywhatmechanismdoeshyperkalemia produce each of the effects on the ECG?
   
6. Calcium,insulin,bicarbonateandepinephrinewereadministeredtothis patient in an attempt to abort the deleterious cardiac effects of the hyperkalemia? By what mechanism(s) does each of these produce a beneficial effect?
   
7. Withinabouta10minperiod,thispatient’splasmapotassium concentration decreased from 9.8 to 4.1 mEq/L. This represents a loss of how many moles of potassium from the plasma? Where did this potassium go?
   
8. Withregardstoquestion7,doesthepotassiumlossfromtheplasma account for all of the potassium loss from the extracellular compartment? Explain you answer. 
   
9. 
   

Answers to Questions Answer to Question 1
Short answer: from skeletal muscle
Long answer: Succinylcholine binds to and activates acetylcholine (ACh) receptors at muscle neuromuscular junctions. Accordingly, it depolarizes the subsynaptic membrane. Since succinylcholine resists hydrolysis by acetylcholine esterase, the depolarization of the subsynaptic membrane is prolonged leading to inactivation of sodium channels in the vicinity of the subsynaptic membrane. By this mechanism, the muscle becomes unexcitable 
inducing a relaxed muscle state. However, increased K- loss from the muscle will occur 

since potassium efflux through open K-channels increases as membrane potential moves 
more positive; difference between membrane potential and potassium Nernst potential 
increases. Succinylcholine produces some K- loss from normal individuals but the effect is 
blunted by the fact that this loss is confined to K-channels near the endplate. The 
hypersensitivity of some individuals to succinylcholine is due to the existence of ACh receptors in extrajunctional areas. The extrajunctional receptors increase the area of depolarized membrane and K-efflux though open K-channels. In some rare cases, succinylcholine induces rhabdomyolysis (i.e., breakdown of the muscle membrane).

Answer to Question 2
Maximum diastolic potential becomes more negative, rate of phase 4 depolarization is decreased, rate of phase 0 depolarization is decreased, and rate of phase 3 repolarization is increased. Bradycardia is related to the more negative maximum diastolic potential and decreased rate of phase 4 depolarization. 

Answer to Question 3
All of these effects are produced by the increase in potassium conductance that occurs in hyperkalemia.

Answer to Question 4
PR interval is increased, RT interval is decreased, and T-wave is increased in magnitude.

Answer to Question 5
The increase in PR interval results from slowed conduction velocity of both atrial and AV-node action potentials. Enhanced K-conductance contributes to both events. In the atrium, increased sodium channel inactivation due to membrane depolarization also acts to slow conduction. The decrease in RT-interval reflects the decrease in ventricular action potential duration caused by increased K-current due to increased K- conductance. The increased magnitude of the T-wave reflects faster phase 3 repolarization caused by increased K-
current due to increased K-conductance

Answer to question 6.

Increased extracellular calcium, in the presence of hyperkalemia, returns excitability related to Na-dependent action potentials towards normal. Extracellular calcium affects the voltage-dependency of sodium channel inactivation (i.e., the position of the inactivation curve on the voltage axis). By increasing extracellular calcium, some sodium channels that were inactivated by the hyperkalemia-induced depolarized state of the membrane are converted to the resting state. The recovery of resting sodium channels acts to return excitability toward normal. Increased calcium produces this effect by shifting the sodium channel inactivation curve toward more depolarized potentials.

Bicarbonate acts to return excitability towards normal by shifting potassium into the cell from the ECF thereby shifting resting potential more negative. By reducing extracellular hydrogen ion concentration, bicarbonate enhances sodium transport into the cell via the Na-H exchanger. The increased Na-influx acts to increase intracellular sodium ion concentration. In turn this enhances Na-K pump thereby moving potassium into the cell. 

By stimulating the Na-K pump, insulin also acts to move potassium into the cell.
Epinephrine acts to restore heart rate and AV-node conduction towards normal. It does this by increasing the funny sodium current responsible for phase 4 depolarization in SA-node cells. It also increases L-type calcium current thereby increasing the rate of phase 0 depolarization in AV-node cells (also in SA-node cells). This increases action potential conduction velocity of these cells.

Answer to Question 7

Since interstitial and plasma potassium concentration are in equilibrium, the concentration of potassium in the ECF must be reduced by 5.7 mEq/L in order to reduce plasma potassium concentration from 9.8 mEq/L to 4.1 mEq/L.
ECF volume is about 20% (i.e., body weight x 0.6 x 0.33) of total body weight. For the patient in this case this would be about 23 liters. A loss of about 131 mEq (23 x 5.7) from the ECF would be required to reduce ECF potassium concentration by 5.7 mEq/L. Since the kidneys cannot excrete this much potassium in 10 minutes (daily excretion of potassium by the kidneys is about 95 mEq), it seems reasonable to conclude that the potassium went into cells.
NOTE: The assumption used in the above calculation that ECF is 20% of total body water will overestimate ECF in this patient who is most likely obese (251 lbs). A more realistic ECF is about 20.3 liters which is obtained assuming this patient has 25% body fat. Using the more accurate estimate of ECF volume, the loss of potassium from the ECF is still greater than the daily rate of potassium excretion via the kidney.

Answer to Question 8

Since the interstitial compartment, rather the plasma compartment, is contiguous to cell membranes, the movement of potassium into cells requires the movement of potassium out of the interstitial compartment and into the cell. The reduction of plasma potassium from 9.8 to 4.1 mEq/L requires that interstitial potassium concentration be reduced by a similar amount. Since the interstitial compartment is about 3-fold larger than the plasma