Sedation and Neuromuscular Blockade

As mentioned above, most patients require sedation in order to tolerate mechanical ventilation. It can be a frightening experience; not only do they have a very large tube in their throat, but they can’t even control their own breathing. Patients who are mechanically ventilated for more than a few days may be used to it enough to remain calm and follow commands once they’re aroused, but they still need frequent reassurance that they’re being closely monitored and that their needs will be met.

Common Medications

Medications used during mechanical ventilation fall into four categories: sedatives, neuroleptics, analgesics, and paralytics.

Sedatives include benzodiazepines, barbiturates, and propofol. These drugs decrease anxiety and produce amnesia, but they don’t relieve pain. Most of these drugs also have anticonvulsant effects without causing cardiac depression. The exceptions to this are midazolam (Versed) and propofol (Diprivan), which can cause cardiac depression.

The primary concerns related to use of sedatives during mechanical ventilation are that many have long half lives, and that drug levels can accumulate and cause prolonged effects in the critically ill and elderly. This is particularly true of the barbiturates, and may negatively impact weaning attempts. Midazolam (Versed) has the shortest half life of the benzodiazepines (1 hour), thus it is the most commonly used. The other benefit to benzodiazepines is that their effects can be reversed with flumazenil (Romazicon).

Most patients require sedation in order to tolerate mechanical ventilation.

One precaution should be mentioned regarding midazolam (Versed). It tends to accumulate in the tissues if administered for longer than 48 hours, and can cause excessive sedation. This is especially true of obese patients because of the lipophilic properties of the drug and the high degree of lipid solubility. In obese patients, the ideal body weight should be used to calculate dosing, rather than the actual weight.

Propofol (Diprivan) is the sedative of choice for rapid induction of anesthesia in the ICU for minor invasive procedures. It has a rapid onset and a half-life of less than 30 minutes. However, it often causes hypotension and is very expensive.

Dexmedetomidine (Precedex) is a short-acting alpha agonist approved by the U.S. Food and Drug Administration in 1999 for use as an ICU sedative. It has anxiolytic, anesthetic, hypnotic, and analgesic properties, and can be given even during ventilator weaning. Patients receiving an IV infusion can be easily aroused, yet return to a hypnotic state when not stimulated. These properties make it an ideal drug for ventilator-dependent patients, but it's also very expensive.

The following is a summary of the most common sedatives given as a continuous infusion.

  Lorazepam Midazolam Propofol Dexmedetomidine
Trade name

Ativan

Versed

Diprivan

Precedex

Onset of action

5-15 minutes

1-3 minutes

1 minute

Immediately

Half-life

6-15 hours

1 hour

< 30 minutes

1.5-3 hours

Loading dose

0.05 mg/kg

0.03 mg/kg

0.5 mg/kg

1 mcg/kg

Infusion rate

0.5-5 mg/hr

1-20 mg/hr

0.5-3 mg/kg/hr

0.2-0.7 mcg/kg/hr

In addition to sedation, neuroleptics may be given to patients who are experiencing delirium or “ICU psychosis.” This is common in critically ill patients who lose sense of time and events because of altered sleep patterns and a different daily schedule while they’re hospitalized. Symptoms include disorganized thinking, audio and visual hallucinations, and disorientation. Sedatives and narcotics often worsen the delirium because they further alter sensory perception. The neuroleptic drug of choice is haloperidol (Haldol). It’s usually given intravenously in 2-10 mg doses every 2 to 4 hours. Effects should be observed within 30-60 minutes. Haloperidol can prolong the QT interval on the EKG, and should be used cautiously in patients who are at risk for QT prolongation from other causes.
Analgesics should be prescribed for every patient receiving mechanical ventilation. Because sedatives reduce many of the emotional signs of pain, medical personnel may overlook the fact that the patient is still experiencing the physical component of pain. Intravenous narcotics are the analgesic of choice for this patient population because they exert their effect on the central nervous system, rather than only the peripheral pain receptors. Morphine is preferred unless the patient has cardiovascular instability. In this case, the patient may not tolerate the transient hypotension produced by morphine-related histamine release, so fentanyl (Sublimaze) or hydromorphone (Dilaudid) can be used instead.

If a patient receives large or continuous doses of narcotics, they must be monitored for the development of ileus. Tolerance of tube feedings and bowel movements should be assessed frequently.

Paralytic agents, or neuromuscular blocking agents (NMBs), are used to paralyze a patient in order to allow controlled mechanical ventilation. However, these drugs do not have any sedative or analgesic effects, so they must always be administered with other sedatives and narcotics. Imagine being fully awake and able to feel pain...but paralyzed!

There are two classes of NMBs: nondepolarizing (inhibit acetylcholine) and depolarizing (prolong depolarization of the postsynaptic receptors). The depolarizing agents have a short duration of action and are used for short-term paralysis during intubation. Succinylcholine (Anectine) is a depolarizing agent. The nondepolarizing agents produce prolonged paralysis and are used for controlled mechanical ventilation. Examples include cisatracurium (Nimbex), pancuronium (Pavulon), and vecuronium (Norcuron), among others.

Peripheral Nerve Stimulator

Patients who require long-term neuromuscular blockade must be closely monitored to prevent complications, such as prolonged skeletal muscle weakness. The patient’s level of paralysis is assessed with a peripheral nerve stimulator (PNS). This is a device that delivers an electrical stimulus to a preselected nerve. Usually the ulnar nerve is used, although the facial, posterior tibial, or peroneal nerves are also options. Pre-gelled electrodes (often the same as those used for cardiac monitoring) are attached to the patient’s skin and the current is delivered through them.

The methods of testing the level of paralysis include single, tetanic, and train-of-four (TOF). TOF is the most common and involves delivering four consecutive electrical stimuli. When the ulnar nerve is used, the expected response is twitches of the thumb toward the hand. The number of twitches corresponds to the level of paralysis: four indicates 75% blockade; three twitches, 80%; two twitches, 85%; one twitch, 90%; and none indicates 100% blockade. Generally, the desired goal is one twitch, or 90% blockade.

It’s very important to test the patient’s baseline TOF prior to administering the NMB. The amount of electrical current delivered is controlled by the milliamp (mA) dial. Find the patient’s baseline by starting at 10 mA and increasing by 10 mA until four strong twitches are achieved (most patients require approximately 30 milliamps), then double that number for testing TOF after administration of the NMB (usually close to 60 milliamps). The mA should never be set at less than 40 mA or greater than 100 mA for testing TOF while the patient is receiving the NMB. After initiation of the NMB, the TOF should be checked and recorded every 15-30 minutes until a steady state is achieved, then every two hours for the first 24 hours. If the infusion is continued longer than 24 hours, the TOF can be checked every four hours unless the NMB is being titrated.

Other factors can affect the results of the PNS. Poor skin contact with the electrodes, improper electrode placement, serum electrolyte imbalances, and edema can result in false twitch responses, leading to underestimation of the degree of paralysis, or no response, leading to overestimation of the degree of paralysis. False responses may lead to incorrect dosing of the paralytic agent, thus the PNS test should be correlated to observations of patient movement.

Connecting the PNS to the Patient
Connecting the PNS to the Patient

Critical Illness Polyneuropathy

One final note must be made related to the use of NMBs. Critical illness polyneuropathy is primary axonal degeneration of motor and sensory fibers, denervation atrophy of muscles, impaired tendon reflexes, and damaged muscle membranes resulting from long-term use of NMBs. Patients with diabetes or who are receiving large doses of steroids are especially at risk for polyneuropathy. Weakness can last for months and is not reversed by cholinesterase inhibitors. Prolonged nerve block without damage can occur in patients who are receiving large doses of steroids and in those with renal failure or sepsis, related to an inability to metabolize and excrete the NMBs. Patients often develop tolerance to the NMBs over the course of several days, and the dosing must be increased to have the desired effect, which increases the risk of polyneuropathy. In the ICU, it’s recommended that NMBs only be used when sedatives and analgesics have failed to provide controlled ventilation, and that they not be used for more than 24 hours in patients with renal failure, sepsis, or on high doses of steroids.

Drug Medication Classes

Drug

Class

midazolam (Versed)
cisatracurium (Nimbex)
morphine
haloperidol (Haldol)
propofol (Diprivan)
succinylcholine (Anectine)

sedative (benzodiazepine)
paralytic (nondepolarizing)
analgesic (narcotic)
neuroleptic
sedative
paralytic (depolarizing)


Case Study

At 1330, Mr. Hill’s wife asks for you at the nurses' station. She tells you that Mr. Hill seems very anxious, and that she’s been holding his hands so he doesn’t pull out the tube. You follow her to the room and find Mr. Hill with his legs hanging off the side of the bed and his hand on the ventilator tubing. His respiratory rate is 30 and the ventilator is alarming with almost every breath. Per the pulmonologist’s order, you administered 2 mg of Versed at 1200 and 1300, but Mr. Hill’s anxiety seems worse instead of better. He looks at you when you talk to him, but doesn’t respond appropriately or follow commands. Another nurse helps you settle him in bed again and you ensure that his wrist restraints are secure before leaving the room to call the physician.

Question Answer

1. What do you anticipate the physician will order?

A continuous Versed infusion and possibly neuromuscular blockade.

The physician orders a continuous Versed infusion of 1-10 mg/hr, titrated to effect, and a Nimbex infusion with TOF maintained at 90%.

Question Answer

2. The physician is ready to hang up the phone, but you think of one more crucial thing to ask him about the ventilator settings. What is it?

The ventilator mode is currently SIMV, which is used with spontaneously breathing patients. However, the Nimbex infusion will paralyze Mr. Hill’s diaphragm along with the rest of his body, thus the ventilator mode should be changed to completely take over respiratory function. The mode should be changed to control or assist-control ventilation.

3. Which infusion will you start first, the Versed or the Nimbex?

Versed. Remember that NMBs do not have any sedative or analgesic properties. Always sedate the patient prior to administering a paralyzing agent.

4. How will you monitor the level of paralysis?

Test train-of-four (TOF) with a peripheral nerve stimulator. Remember to test and record the baseline prior to starting the Nimbex. After the infusion is started, test TOF every 15 –30 minutes until steady state is achieved. Then it may be tested every two hours for the first 24 hours, unless the Nimbex is being titrated. The physician ordered 90% blockade, so the goal is one thumb twitch.

5. How will you explain this change in events to Mr. Hill’s wife and family?

Keep the explanation simple but be sure to answer their questions. Keep in mind that the word "paralysis" may frighten them. Important points to include are: the paralysis is caused by medication and is reversible, the paralysis is only a temporary measure to help Mr. Hill breathe better with the ventilator, and his level of paralysis will be closely monitored with the PNS. Tell them that he is sedated, but encourage them to talk to him and touch him. Also reassure them that Mr. Hill’s physical needs such as repositioning, oral care, and bathing will be taken care of by the staff.



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