Rapid sequence induction is increasingly used in emergency departments as a safe and effective way to manage patients who need intubation emergently. This Cyberounds^® presentation will discuss the technique of rapid sequence induction in the emergency department, concentrating particularly upon the indications and contraindications of the drugs used in this procedure. This discussion will not include detailed information about the indications for intubation, nor about the procedure of intubation itself.

With these thoughts in mind, let's consider several typical patients that might appear in an emergency department and how you would manage them.

Patient Number One

The first patient is a 32-year-old trauma victim with a head injury and pelvic fractures. He has a blood pressure of 100 mm Hg systolic and needs intubation prior to going to the CT scanner.

Patient Number Two

The next patient is a 75-year-old patient who has chronic respiratory disease and has spent the past three days lying on the floor. He has a fracture of the hip, is now in severe respiratory distress and needs intubation.

Patient Number Three

A child of four, she has a head injury and requires helicopter transport. She is hemodynamically stable at this time.

Q. What IS the definition of rapid sequence induction?

A. Rapid sequence induction is a method of paralyzing and intubating a patient who, potentially, has a full stomach.

Rapid sequence induction comprises a series of steps that always need to be followed in order. Rapid sequence induction is designed to facilitate intubation by rapidly sedating and paralyzing the adequately pre-oxygenated patient, attenuating the normal pathophysiological reflexes associated with direct laryngoscopy and tracheal intubation, and reducing the risk of aspiration of gastric contents into the lungs.

It is important to note that in RSI the sedative and paralyzing drugs are given by rapid push, one after the other. This technique produces a rapid onset of sedation and paralysis and reduces the length of time that the patient is potentially apneic.

Some use mnemonics to help them remember the stages of procedures.

Q. What mnemonic will help you remember the stages in rapid sequence induction?

A. One mnemonic that can be used is the use of the letter 'P':

Prepare
Pre-oxygenate
Pre-treat
Prime
Pressure
Paralysis
Placement

Preparation is very important. There are few procedures performed in the emergency department that do not benefit from preparation. In the case of intubation, preparation, both of equipment and staff, is vital. Everyone present needs to understand his or her roles in order for the procedure to run smoothly.

Q. What do you check prior to performing an intubation?

A. Ensure that:

1. The cuff on the endotracheal tube is not ruptured
2. The suction is working efficiently
3. The laryngoscope has a fully functioning light and the bulb is firmly screwed in
4. A spare laryngoscope, alternative blades and at least one spare endotracheal tube are readily to hand
5. The drugs are drawn up ready and the syringes are labeled
6. The nursing staff understands which drugs to give and when
7. There is one person responsible for performing cricoid pressure and they are certain of the correct method of performing the Sellick maneuver. This maneuver will be discussed in detail later in this Cyberounds^®.

Although this seems like a long list, in fact it can be done in a few moments. This is especially true if the nursing and ancillary staffs have been trained in the procedure, and are familiar with the drugs used and their method of administration.

Pre-oxygenate. This stage is very important to the safe and effective use of rapid sequence induction. Pre-oxygenation is the establishment of an oxygen reservoir in the lungs and the body tissues. This reservoir will ensure satisfactory oxygen saturation despite several minutes of apnea. In fact, the normal 70 kg adult will maintain oxygen saturation above 90% after as long as eight minutes of apnea.(1) An obese adult, weighing about 125 kg, will desaturate much more quickly - only staying above 90% for two or three minutes. A moderately ill, 70 kg adult will also desaturate more quickly than a previously healthy 70 kg adult, taking about five minutes to drop below 90%.

It is important to remember that the oxygen dissociation curve drops sharply after about 90%, and the time to get from 90% to zero is much shorter than the time to get from 100% to 90%.

An essential feature of preoxygenation is the avoidance of active 'bagging' of the patient. Why? The premise behind rapid sequence induction is that the patient may well have a full stomach. Active 'bagging' of the patient (who is still breathing spontaneously) runs the risk of inflating the stomach with air and thus increasing the chance of aspiration. A bag-valve-mask set-up is used to provide as close to 100% oxygen as possible. This is applied for five minutes - time for the build up of an oxygen reservoir. The mask needs to be held tightly to the face to produce an adequate seal -- this may require the assistance of another pair of hands. It is again stressed that if the patient is breathing spontaneously, they should not be actively bagged.

In some circumstances, it is not possible to wait for the full five minutes. In these cases, the patient can be instructed to take 8-10 full vital capacity breaths rapidly, while breathing 100% oxygen. This will have nearly the same effect as five minutes of normal respiration.

Pre-treatment. Common agents used in this phase include lidocaine, opiates, atropine and defasciculation doses of a non-depolarizing muscle relaxant.

Q. What is the rationale for the use of pretreatment agents and when should they be used?

A. Pretreatment agents do not need to be used routinely, but rather for specific indications when appropriate.

Lidocaine has two main indications. First, through its action in suppressing cough and attenuating the increase in airway resistance, noted especially in patients with reactive airways disease when being intubated. Second, lidocaine blunts the rise in intracranial pressure seen during intubation and, thus, is useful in patients for whom further increases in intracranial pressure would be potentially harmful, for example those patients who have had a significant head injury or a possible intracranial bleed. The usual dose is 1.5 mg/kg intravenously.

Opiates are administered to attenuate the sympathetic responses that occur with intubation. Patients for whom an increase in heart rate or blood pressure could be a potential problem benefit from opiates. Examples might include patients with a suspected aortic aneurysm or with underlying myocardial ischemia.

Fentanyl is a frequently prescribed opiate. This drug is short acting and does not cause histamine release. The dose in this setting is usually about 3 ug/kg. This should be the last of the pretreatment drugs given and should be administered over 30-60 seconds. Side effects may include hypotension and respiratory depression.

Q. What other significant side effect of fentanyl are you aware of and how could it be prevented?

A. Muscular rigidity is a potential side effect. It is usually only seen in doses of greater than 500 mg and in cases where the drug is administered rapidly. It is NOT reversible with naloxone. The chest and abdominal muscles are those most frequently affected.

This complication can be prevented by using the doses recommended above, given slowly. It can also be prevented by use of a defasciculating dose of medication prior to administration. A paralyzing dose of succinylcholine will also reverse it (though, clearly, then intubation is immediately required!). It is worth noting that there have been few if any reports of this complication occurring in the emergency department.

The next agent to consider in the pretreatment phase is atropine. Atropine is indicated in two situations. First, all children under the age of about 10 years should receive a dose of atropine because stimulation of muscarinic receptors, following the administration of succinylcholine, may cause significant bradycardia in children. In adults, this is usually not a problem, except in one circumstance, and this constitutes the second indication for atropine -- when an adult is given a second dose of succinylcholine closely after the first -- as may occur, for example, during a difficult intubation. The dose for children is 0.02 mg/kg.

The final pretreatment agent to be considered is the use of a defasciculating dose of a non-depolarizing muscle relaxant. The use of succinylcholine causes fasciculations due to nicotinic acetylcholine receptor stimulation. These fasciculations are thought to be the cause of the increased intracranial pressure, increased intra-orbital pressure and increased intra-abdominal pressure seen with this agent.

A defasciculating dose of a non-depolarizing muscle relaxant tends to prevent the fasciculations and attenuate the rise in intra-cavitary pressure. Interestingly, it does not seem to always prevent the muscular pain often complained of by patients after the use of succinylcholine, and thought to be due to muscle spasms. The usual defasciculating dose of muscle relaxant is one tenth of the usual paralyzing dose of the agent of choice. For example, one would give 0.01 mg/kg of vecuronium or pancuronium, or 0.1 mg/kg of rocuronium.

These agents are used when a rise in intra-cavitary pressure would be problematic. The classic example is raised intracranial pressure but defasciculating pretreatment should be considered in cases of possible penetrating intra-abdominal wounds. Defasciculating doses of medication are never indicated in children age five years and under.

Priming. By 'priming' is meant the use of sedative agents. Sedative agents are used for a number of reasons. First, it is inhumane and psychologically traumatic to induce paralysis in awake and aware patients. Second, paralysis alone does not attenuate the hemodynamic responses to intubation. During intubation, there is a rapid rise in circulating catecholamines, resulting in tachycardia and hypertension. Sedation helps to partially reduce this response.

Q. What would you consider to be the features of an 'ideal' sedative agent for RSI? Which drug has these properties?

A. The ideal sedative agent would have a rapid onset of action, and act in a predictable and dependable manner with no residual drowsiness or other side effects. The drug would have a wide therapeutic margin of safety. There would be no deleterious effects on hemodynamic stability and no significant other effects, such as a rise in intracranial pressure or histamine release. It would have no significant drug interactions.

Unfortunately, no one drug yet shares all these desirable properties. Thus, there are probably three or four sedative drugs one should be familiar with for sedation during RSI.

The drugs most often used are thiopental, midazolam, (or another benzodiazepine), and most recently etomidate.

Thiopental is a barbiturate that acts upon the GABA-receptor complex. It is classically described as cerebro-protective and is traditionally used in patients with, or at risk for, increased intracranial pressure. A negative aspect of the pharmacological profile of thiopental is that it is a venodilator and myocardial depressant, causing significant hemodynamic instability. In the SHRED study,(2) thiopental produced a mean reduction in systolic pressure of 38.1 mm Hg and a mean reduction of diastolic pressure of 18.3 mm Hg. It should, therefore, be avoided in patients with significant hemodynamic instability.

It should be given in reduced dose to the elderly. Children require a slightly greater dose per kg than adults (5-8 mg/kg for children as opposed to 3-5 mg/kg for adults). Thiopental is completely CONTRAINDICATED in patients with acute intermittent porphyria or with variegate porphyria, as it can precipitate an attack.

Midazolam is probably the most widely used benzodiazepine sedative in RSI. Other benzodiazepines that are used include diazepam and lorazepam. Midazolam has an advantage in that it has a more rapid onset and offset of action compared with diazepam and lorazepam. There is some decrease in blood pressure associated with the use of benzodiazepines, but this is much less than that described with thiopental. Again, in the SHRED study the reduction was a mean of 7.1 mm Hg systolic and 2.6 mm Hg diastolic for midazolam. The dose is usually about 0.2 mg/kg.

A newer agent that has significant apparent advantages is etomidate. It appears to cause little hemodynamic instability, has no adverse effect upon intracranial pressure and does not cause histamine release. It is administered at a dose of 0.2-0.3 mg/kg. The onset of action is usually within about 20-30 seconds and sedation lasts about 7-14 minutes.

There are side effects from the use of etomidate that should be mentioned. (I did say that there are no truly ideal agents yet!). Almost 40% of patients will experience some nausea or vomiting on awaking. Although this is not usually a problem in the emergency department, as patients are often kept sedated and intubated for some time, it is a problem if the patient is to be intubated and then extubated rapidly. Vomiting should be expected in this situation.

Another side effect is that, as patients recover from the medication, they will often experience myoclonic jerks. This could be confused with seizures if one was not aware of this effect. The myoclonic jerking requires no therapy and they rapidly abate.

Pressure. This is where the 'Sellick's maneuver' is used.

Q. What exactly IS 'Sellick's maneuver? And what's this BURP thing?

A. Sellick's maneuver is also known as cricoid pressure. The cricoid cartilage is the only complete ring in the airway. The aim of cricoid pressure is to place backward pressure on the cricoid so that it presses against the esophagus. Such pressure reduces (but does NOT eliminate) the risk of gastric contents refluxing up the esophagus and into the lungs. The pressure applied should be equivalent to pressure placed across the bridge of the nose sufficient to cause discomfort but not pain.

The 'BURP' thing is another mnemonic used to help the applier of the pressure remember the correct technique. The initials stand for Backwards Upward Rightward Pressure. This improves the alignment of the larynx for a right-handed laryngoscopist and is thought to make intubation a little easier.

Finally, the time has come to paralyze the patient. The most common agent used for paralysis is succinylcholine, a depolarizing neuromuscular blocker.

Q. What are some of the contraindications for the use of succinylcholine?

A. Succinylcholine is close to being an ideal agent for use in RSI. It has a rapid onset of action, causing paralysis within about 45 seconds. It lasts usually less than 10 minutes. It is actually two molecules of acetylcholine joined together end to end. It is rapidly hydrolyzed by plasma cholinesterases. Only a small amount of the original drug actually reaches the neuromuscular junction. There is little or no cholinesterase present at the junction and thus action of the drug is ultimately terminated by its diffusion away from the motor end plate.

Some patients, those with an abnormal variant of plasma cholinesterase, are at risk for prolonged paralysis from the use of succinylcholine. However, this is a rare problem. The management is to support the patient until the drug eventually wears off, which may take many hours.

Other effects from this medication are potentially serious. Patients will experience muscular fasciculations when the drug is first administered. These fasciculations are thought to be the cause of the rise in intracranial, intra-ocular and intra-abdominal pressure seen with this agent. It is theorized that the fasciculations result from nicotinic acetylcholine receptor stimulation. If the patient is at risk for raised intracranial pressure, a defasciculating dose of a non-depolarizing muscle relaxant is indicated in the pre-treatment phase, as discussed above.

All patients who are given succinylcholine will experience a rise in serum potassium. The rise is due to release of potassium from depolarized myocytes. A rise of 0.5 mEq/L can be expected on average. However, there are some patient populations who are at risk for significantly greater rises in serum potassium - in some cases rises of 5-10 mEq/L. These patients are likely to develop potentially fatal cardiac dysrhythmias the treatment of which may be very difficult.

Q. Which patients are particularly at risk from a significant rise in serum potassium?

A. Patients with the following problems are at risk of hyperkalemia if given succinylcholine:

• End stage renal disease

The risk in this patient population is theoretical but case reports do exist. Many patients with renal failure are intubated using succinylcholine without problems. In the emergency department, where the patients' potassium levels are often unknown, it may be prudent to use alternative agents.

• Severe metabolic acidosis
• Severe rhabdomyolysis
• Muscular dystrophy, for example, Duchenne's
• Sub-acute spinal cord injury

Patients with an acute spinal cord injury can be given succinylcholine. However, from about seven days after injury until as long as six months post injury, they are at risk from life threatening hyperkalemia. The same is true for patients who have suffered an acute stroke.

• Burn patients

From about 24 hours after the burn, the patient is at risk for hyperkalemia. It is important to note that the extent of the burn is not related to the degree of hyperkalemia -- clinically important hyperkalemia has been reported (though rarely) in patients with as little as 10% body surface area burns. The length of time after the burn that the patient is at risk is highly variable and is dependent upon healing. It is prudent in patients with extensive burns to avoid the use of succinylcholine for one to two years after the acute burn has healed.

• Patients with extensive crush injury

Although there is a paucity of information in this area, it appears that there is a risk of significant hyperkalemia from about five to seven days after the crush injury to as long as 60-90 days, depending upon the extent of the initial injury.

Another problem with succinylcholine occurs in children, and also in adults who are given two doses 'back-to-back'. In these cases, stimulation of the muscarinic receptors causes bradycardia. This fact explains the use of atropine as a routine mediction in all children under the age of ten, as well as in adults when a second or subsequent dose of succinylcholine is required.

Malignant hyperthermia is a well known risk. This condition, which is initially marked by muscle rigidity, hypoxia, hypotension, autonomic instability, hyperkalemia, disseminated intravascular coagulation, lactic acidosis, and only later by hyperthermia, is very rare. The onset of the condition can be acute, but occasionally it can be delayed for hours. It has not yet been reported in relation to the use of succinylcholine in emergency departments.

Should you be unlucky enough to be the first to experience this complication, the initial treatment is rapid and aggressive cooling, and dantrolene, 2.5 mg/kg every five minutes to a maximum of 10 mg/kg, which should be given as soon as the possibility of this diagnosis is raised.

Information about malignant hyperthermia can be obtained from the Malignant Hyperthermia Emergency Hotline at 1-800-644-9737.

If the patient cannot, for any of a number of reasons, be given succinylcholine, what are the alternatives?

Several non-depolarizing muscle relaxants are available. One relatively new agent is rapacuronium. This agent has duration of onset equivalent to succinylcholine but lasts about 20 minutes. However, it can be reversed by the use of neostigmine (0.05 mg/kg) and glycopyrrolate (0.01 mg/kg) or atropine. However, these agents are only effective after some recovery has started to occur, usually, with this agent, after about 10 minutes. It has little effect on hemodynamic status, though provokes more than occurs with succinylcholine. It does not have the other adverse effects (on potassium or intracranial pressure, for example) that are seen with succinylcholine.

Another agent that has been used is rocuronium. This has a slightly slower onset of action than rapacuronium and lasts longer -- 40-60 minutes. It can only be reversed after about 20 minutes and causes little hemodynamic instability.

Finally, there is vecuronium, which has minimal side effects but has a slower onset of action. Paralysis lasts for 30-40 minutes. The time to onset of action can be shortened by using a larger dose (0.3 mg/kg rather than the 'standard' 0.1 mg/kg) but this comes at the cost of prolonged paralysis -- as long as 100 minutes. Another way to reduce time to onset can be achieved by giving a small 'defasciculating' dose (0.01 mg/kg) in the pretreatment phase and then giving a slightly larger dose (0.15 mg/kg) at the time of paralysis.

Now we have a preoxygenated, sedated, paralyzed, patient. Time for the last 'P':

Placement, and hopefully success!

So, now is a good time to review and to put it all together. Let's consider the three patients introduced initially and work through the procedure for each of them.

The first patient of the day is a 32-year-old trauma victim with a head injury, and pelvic fractures. He has a blood pressure of 100 mm Hg systolic. He needs intubation prior to going to the CT scanner.

Q. How would you manage this patient's RSI?

A.

1. Start:
   • Preparation
   • Start preoxygenation with 100% oxygen via bag valve mask
2. One minute:

   Pretreatment -- in this case (due to the risk of increased intracranial pressure) consider the use of lidocaine and a defasciculating dose of a competitive non-depolarizing neuromuscular blocking agent

3. Four minutes:
   • Administer sedatives -- in this case etomidate would be appropriate in view of his hemodynamic status
   • Apply cricoid pressure
   • Administer paralytic agent -- succinylcholine would be appropriate
4. Five minutes:

   Intubate. Check placement. Remove cricoid pressure.

The next patient is a 75-year-old who has chronic respiratory disease and has spent the past three days lying on the floor. He has a fracture of the hip and is now in severe respiratory distress. He needs intubation.

Q. How would you intubate this poor chap?

A.

1. Start:
   • Preparation
   • Start preoxygenation with 100% oxygen via bag valve mask
2. One minute:

   Pretreatment -- in this case (due to the past history of respiratory disease) consider the use of lidocaine

3. Four minutes:
   • Administer sedatives -- again, I would use etomidate here, although midazolam would be a completely acceptable alternative
   • Apply cricoid pressure
   • Administer paralytic agent - succinylcholine would NOT be appropriate in this case because of the risk of rhabdomyolysis from the prolonged period lying on the floor. I would use rapacuronium if available or rocuronium if not.
4. Five - Six minutes:

   The difference in the time is related to the slightly slower onset of action of these agents. Intubate. Check placement. Remove cricoid pressure.

The final patient was a four-year-old with a head injury who requires helicopter transport. She is hemodynamically stable at this time.

Q. What would be the schema for this girl?

A.

1. Start:
   • Preparation
   • Start preoxygenation with 100% oxygen via bag valve mask
2. One minute:

   Pretreatment -- in this case (due to the risk of increased intracranial pressure) consider the use of lidocaine, although this agent is not widely used in children. Also, both in view of the fact that we can plan on using succinylcholine and that the child is having manipulation of the airway and is under the age of five, we need to give atropine. A defasciculating dose of medication is NOT given to children under the age of five years and so we would not use this.

3. Four minutes:
   • Administer sedatives -- again, in this case, etomidate would be appropriate in view of her head injury. Thiopental would be a very reasonable alternative.
   • Apply cricoid pressure
   • Administer paralytic agent -- succinylcholine would be appropriate at a dose of 2.0 mg/kg
4. Five minutes::

   Intubate. Check placement. Remove cricoid pressure.