Sedation

Analgesics are drugs that relieve pain without the patient losing consciousness. It is important to understand that most analgesics can, in the face of increased dosage or when mixed with other CNS depressants, result in unconsciousness. Systemic analgesics run the gamut from oral aspirin to lower doses of morphine.

· Acetaminophen [Tylenol] is a common OTC analgesic agent that can also decrease fever. Worse side effect of acetaminophen is liver damage, particularly when this drug is used with alcohol.

Anti-inflammatory agents such as oral non-steroid anti-inflammatory agents, and less often, oral steroids are used as analgesics when pain is caused by inflammation pressing on pain receptors. These drugs inhibit the conversion of arachidonic acids into prostaglandins. In addition to their analgesic activity, many of these drugs are anti-pyretic.

· Side effects of NSAIDS include gastric upset, renal failure and peptic ulcers.

Anti-spasmodics / muscle relaxers are used for analgesics when the pain is related to muscle spasm such as during trauma or associated with some neuromuscular disorders.

· Example of a muscle relaxer is low-dose Diazepam [Valium]. These drugs seem to work by CNS depression or sedation.

· Side effects of muscle relaxation is drowsiness, dizziness and physical dependence.

Anesthetics are a class of drugs that are used to suppress pain. When given systemically, these drugs might render the patient unconscious, but when given locally, an anesthetic blocks impulses along the axons coming from an area. The patient may feel pressure but not pain.

· Injectable anesthetics such as those in the barbiturate family are used to induce anesthesia. These are frequently used with the inhaled anesthetics for general anesthesia. In large doses, administration results in unconsciousness and amnesia. Drugs in this class include diazepam (Valium), midazolam (Versed), and Propofol (Diprivan.) These drugs are also classified as anti-anxiety agents, hypnotics and as sedatives

o Side effects of these systemic anesthetics include respiratory, cardiovascular depression and respiratory arrest.

o Diazepam (Valium) and midazolam (Versed), commonly used with mechanically ventilated patients, are less likely to cause cardiovascular depression than other drugs in their class.

· Opiates are systemic anesthetics that arise from opium. This is a large family that includes morphine and codeine. Many cough suppressants include codeine which makes their use dangerous for the severe respiratory patient because the resulting CNS depression can mask respiratory failure. While effective and useful, this class of drugs is highly addictive.

o During morphine IV infusions, systemic blood pressure and HR parameters need to be monitored and maintained.

o Morphine is used during an MI to control the pain of infarcted myocardium and as a vasodilator to decrease the work of the heart

Reversal of opiates is accomplished by giving a drug called naloxone [Narcan] However, once the naloxone wears off, if the opiate hasn’t worn off, the patient may relapse back into unconsciousness.

· This drug will not reverse the non-opiate sedatives and anesthesia agents. In excessive doses, this drug can cause ventricular tachycardia or ventricular fibrillation resulting in cardiac arrest.

Inhaled anesthetics are never given by the RCP. For the most part only an anesthesiologist or a certified nurse-anesthetist is allowed to handle these dangerous drugs. Inhaled anesthetics include such drugs as nitrous oxide [laughing gas] & halothane.

· The devices used to deliver anesthesia gases are essentially mechanical ventilators that both titrate and deliver the drug and support the patient once his respiratory drive has been depressed. Inhaled anesthetics must be scavenged and removed from the operating room so that the surgeon & other staff will not fall victim to the drugs’ effects.

· Most of the inhaled anesthetics are flammable and the older ones were explosive, so handling them is tricky. OR staff must wear static-free shoe covers and cotton scrubs to avoid static electricity.

· side effects: Inhaled anesthetics have dangerous side effects such as suppression of ventilation, inability to protect the airway and decreased cardiac function and blood pressure. Patients getting inhaled anesthetics are subject to nausea and vomiting sometimes for hours after a procedure. This is the major reason why pre-op patient are NPO the night before a surgery and for hours afterwards.

· Many of these drugs can make patient more sensitive to endogenous catecholamine, thus can trigger cardiac arrhythmias.

· One of the older inhaled anesthetics causes increased incidents of miscarriages in the wives of the male anesthesiologists.

· Rarely, a patient may get a lethal reaction to anesthetics called malignant hyperthermia.

· Patients getting inhaled anesthetics may be mask-bagged for short procedures but intubated for longer ones. They must be constantly assessed by pulse-oximetry, frequent chest assessment of BBS and chest excursion, and by heart monitors and exhaled C0₂ monitors [Capnography.]

Local anesthetics are injected, sprayed on, rubbed into or given by inhalation (SVN or atomizer) to the area that requires anesthesia. Drugs like lidocaine, procaine and cocaine are all local anesthetics used during minor invasive procedures such as placement of arterial lines, oral surgery, intubation, tracheostomy, heart catheterization procedures, endoscope and bronchoscope.

Prior to a bronchoscope procedure, a SVN treatment with lidocaine may be given a few minutes before the tube is advanced. Give the treatment with a mask so that the nasal passage as well as the throat is deadened. The patient losses some sensation in the back of the throat for a few hours, so be careful with food until the patient can feel again.

· Patients who fight the endotracheal tube can be given inline SVN with lidocaine or the lidocaine can be instilled down the tube. Before this is done, the endotracheal tube position must be assured by X-ray and by looking at the placement number. If the tube is down too low it will irritate the carina and pulling it back is the correct action. If that has been done and the patient still bucks the tube and you want the patient awake, instillation of lidocaine is helpful.

· Lidocaine can be injected around the artery prior to arterial stick or placement of an arterial line.

· Lidocaine is also given systemically to treat an irritable myocardium and is commonly used during acute coronary syndromes (MI.)

Anti-anxiety drugs (tranquilizers) are used during procedures to calm a patient and in larger doses to promote a degree of amnesia. These drugs are given about an hour before surgery.

· A new type of anti-anxiety drug has been ok’ed by the FDA for use with mechanical ventilation patients for less than 24 hours. This is Precedex, dexmedetomidine, an Alpha 2 agonist which acts on the receptors involved in the panic associated with the “fight or flight” response. The special quality of this drug is that it has no effect on ventilatory drive, and has a possible future sedating patients who are being weaned off mechanical ventilation. This drug is known to cause bradycardia and cardiac arrest.

Hypnotics are drugs given to promote sleep. Many anti-anxiety drugs become hypnotics when given in high enough doses. Sedation from higher doses of these drugs can result in loss of consciousness, decreased blood pressure and depressed ventilatory drive.

· Many hypnotics will reduce REM sleep, which may have detrimental effects on their mental health

Anti-epilepsy drugs or anti-seizure drugs at lower doses reduce excessive EEG activity without depressing the CNS, but at high doses can start affecting consciousness.

Conscious sedation is a technique of adjusting drug dosages used to perform minor surgery in such a way that the patient never losses consciousness. This technique usually includes both systemic sedatives such as midazolam (Versed) to calm the patient, an anesthesia gas such as nitrous oxide [laughing gas] and the use of local anesthetics to control the pain.

· Conscious sedation is a tricky technique because the occasional patient may slip into true unconsciousness thus losing the ability to protect his airway, or he may begin to hypoventilate.

· There must always be adequate monitoring of the patient by someone not involved with the procedure—such as the RCP. Pulse oximetry and heart monitors are suggested for these procedures. Reassessment of the patient’s LOC is necessary.

Paralytic agents

When patients are in surgery or placed on mechanical ventilation, it is helpful to have not only a drug-induced coma with sedatives and hypnotics, but reduce trauma to the body by drug-induced paralysis. The use of these paralytic drugs means that less anesthetic agents may be used, which means there are lower incidences of side effects.

Neuromuscular blockers will paralyze the skeletal muscles. Relaxed skeletal muscles are less traumatized when cut.

Patients who ‘fight the ventilator’ place themselves at increased risk of barotrauma and they may not get the tidal volumes they need to control their high PaC02.

Many pulmonary patients requiring mechanical ventilation such as asthmatics and persons with ARDS are at particular risk for high airways pressures with mechanical ventilation. When we sedate & paralyze them, we can ventilate them with lower pressures-- thus causing less barotrauma. We can watch the trending of their pressures and sometimes relate this to their level of sedation and paralysis.

Patients on paralytic agents require good oral care because they cannot swallow oral secretions.

It is important to understand that no paralytic agent relieves pain or anxiety. Patient given only paralytic agents will hear and feel everything. These drugs must always be accompanied by a sedation and anesthesia. Because it is difficult to assess the patient’s LOC with these drugs, one must assume that paralyzed patients hear everything we say and we must be careful while speaking around them.

Non-depolarizing neuromuscular blocking agents [or reversible paralytic agents]. In South America, blow gun darts were dipped in Curare to paralyze prey such as monkeys. Death resulted from respiratory failure. If a patient was intubated and ventilated, this same drug action would not be fatal.

· Mode of action: these drugs compete with acetylcholine at the skeletal muscle’s nerve endings. Paralysis results.

· Examples: Non-depolarizing neuromuscular paralytic agents include drugs such as tubocurarine & pancuronium [Pavulon]

· Side effects: paralysis of respiratory muscles lead to death from respiratory arrest, paralysis of upper airway muscle can lead to the inability to protect the airway, and paralysis of gastric muscles can lead to vomiting & aspiration of stomach content. Paralysis of skeletal muscles in the extremities can result in hypotension. Many antibiotics can prolong the paralysis.

· Duration of action: drugs in this family tend to stay active for several hours so these drugs are used to maintain patients in paralysis in the OR and ICU during mechanical ventilation. Full recovery from these agents can take hours

o Antidote to these paralytic agents is neostigmine, which inhibits the enzyme acetylcholinesterase to raise the level of acetylcholine at the neuromuscular junction. This increased Acetylcholine level reverses paralysis.

o Neostigmine is also used to diagnosis a chronic neuromuscular problem called myasthenia gravis. For a few minutes after the drug has been given, the patient’s muscle weakness reverses.

o Neostigmine will not reverse depolarizing neuromuscular blockers; in fact, it will prolong that paralytic drug.

Depolarizing neuromuscular blocking [irreversible paralytic agents]. These agents cause paralysis by causing depolarization of the muscle so that tetany results. The muscle cannot receive another stimulation so paralysis results.

· The drug in this class is succinylcholine [Anectine]

· Duration of action is less than 20 minutes.

· This drug is used to create paralysis for intubation or other short-term procedure. If intubation is unsuccessful, the patient will start breathing again in a few minutes.

· Depolarizing paralytic agents are used to help relax muscles during electroshock to prevent convulsions

· This drug cannot be reversed, but has to wear off.

· Side effects: paralysis of respiratory muscles leads to death from respiratory arrest, paralysis of upper airway muscle can lead to the inability to protect the airway, and paralysis of gastric muscles can lead to vomiting & aspiration of stomach content. Paralysis of skeletal muscles in the extremities can result in hypotension.

· malignant hyperthermia has also been associated with the use of succinylcholine.

· Many antibiotics can prolong the paralysis.

· Some patients have a genetic inability to break down Succinylcholine

· Succinylcholine is contraindicated for patients who have suffered major burns, multiple trauma and upper motor neural damage because it can cause hyperkalemia which can lead to cardiac arrest.

· NOTE that neostigmine will only prolong the duration of depolarizing neuromuscular blockers

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.

One final note must be made related to the use of NMB's. 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 NMB's. 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 NMB's. Patients often develop tolerance to the NMB's 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 NMB's 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.

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