/clinical/,/clinical/references/,/clinical/references/adult-sedation/,/clinical/references/adult-sedation/pharmacology/,

/clinical/references/adult-sedation/pharmacology/

201410293

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UWHC,UWMF,

Patient Care,

Clinical Hub,References,Adult Moderate Sedation Topics

Pharmacology

Pharmacology - Clinical Hub, References, Adult Moderate Sedation Topics

Focus

Note: Patient’s individual response may vary significantly. Ongoing assessment before, during, and after medication administration is essential to determine the patient’s response to the medication. 

Understanding the usual drug dosages, time to onset and peak effect, drug interactions, and duration of action of the commonly used opioids and sedatives is critical to delivering safe sedation. Medication(s) administered for sedation should be titrated until the desired effect is obtained. 

The dosage requirement for sedation generally decreases in the elderly patient, in debilitated patients, those with significant cardiac, pulmonary, or CNS disease and patients with known sensitivity. Total doses and/or frequency of administration may also need to be reduced for patients with renal and/or hepatic dysfunction.

Consider the synergistic properties of medications. A small dose of two drugs acting on different receptor sites may be more effective with fewer side effects than larger doses of one drug. When using these agents in combination, reduce the initial dose of each medication by 30-50% and titrate to the desired effect. Remember to allow time for medications to take effect. 

Opioid Analgesics 

The most commonly used opioid analgesics for short-term sedation include fentanyl, and morphine. You should be familiar with the usual incremental dosage, duration of action, and side effect management of each of these medications. Propofol and other anesthetic agents are not appropriate, nor approved, for use in sedation for procedures by non-anesthesiologists. 

Table A. Opioids for Short-Term Sedation 

Drug

Suggested Usual Dosing

OnsetPeakDuration

Comments

Morphine sulfate IV 1-2 mg increments 2-5 min 15-30 min 30-180 min* May cause histamine release with resultant hypotension, asthma exacerbation
Fentanyl (Sublimaze) IV 25-50 mcg increments 1-2 min 5-10 min 30-180 min* No histamine release; no myocardial depression. 100 times as potent as morphine, note dosage is in mcg
NOTE: Meperidine should not be considered as a choice for sedation and is not approved for this use in the UWHC formulary.

*Duration is dosing dependent, the higher the dose, usually the longer the duration. IV boluses may produce analgesia that lasts as long as IM or SC doses. However, IV boluses produce the highest peak concentration of the drug, and the peak concentration is associated with the highest level of toxicity. 

Opioid Side Effects And Reversal Agent 

Acute side effects of opioids include nausea/vomiting, respiratory depression, rigidity, hypotension, bradycardia, and pruritus. Opioids should be infused slowly over 2-3 minutes to reduce the risk of these effects. 

TableB. Reversal of Opioid Sedative Effects/Overdose 

Drug

Dosing

Onset

Duration

Comments

Naloxone
(Narcan)

 

0.1 - 0.2 mg

Titrate to desired effect.

Comes 400 mcg/1ml, Dilute in 10cc normal saline and give IV push 2-3 ml every 2-3 minutes as needed

1-2 min 30-60 min Duration of action is shorter than most opioids; monitor for resedation in 20 –30 min.

High doses associated with pulmonary edema, ventricular arrhythmia, hypertension, and tachycardia.

Naloxone reverses the effects of respiratory depression, apnea, and sedation caused by opioids.

Benzodiazepines

Benzodiazepines are used to provide the patient with amnesia, sedation, muscle relaxation, and anxiolysis. These medications provide NO analgesia effect. Benzodiazepines can increase the seizure threshold to systemic levels of local anesthetics making seizure less likely. Diazepam and midazolam are metabolized in the liver. 

One of the common side effects of benzodiazepines is over sedation, which may require reversal particularly when respiratory function becomes compromised. It is important to remember the synergistic properties of benzodiazepines and opioids, hence, usually requiring a reduction of opioids and/ or benzodiazepines when the two agents are used concomitantly. By using incremental doses of each type of drug and allowing time for the medications to take effect, one can reduce the overall medication used and the potential for adverse responses due to higher doses of a single agent. 

 Table C. Benzodiazepines for Conscious Sedation 

Drug

Dosing

Onset

Peak

Duration

Comments

Midazolam (Versed)

Short acting.

2.5-5 mg 15 min 15-30 min 1-2 hours Longer duration of action in older adult.

Rapid onset with short duration of action.

3x more potent than diazepam.

Does not cause venous irritation.

Provides antegrade amnesia but not retrograde amnesia

0.5-1.0mg increments IV 1-2.5 min 5-15 min 20-40 min
Diazepam (Valium)

Intermediate acting.

10-20 mg PO 20-30 min 60-120 min 3-4 hours Reduce dose by one third when opioids used concomitantly

Pain with injection. Risk of irritation/phlebitis at injection site.

Longer duration of action in older adult.

Metabolized by the liver; excreted by the kidneys.

2.5-5 mg increments IV 1-5 min 5-15 min 15-60 min
Lorazepam

(Ativan)

Long acting.

2-4 mg IM, PO 15-60 min 60-90 min 12-24 hours Contraindicated with scopolamine but okay with atropine
1-2 mg. IV 20-30 min 45-90 min 6-8 hours

Benzodiazepine Side Effects and Reversal Agent 

Like opioids, benzodiazepines may cause respiratory depression, therefore, frequent assessment is required. These drugs should be administered cautiously in older adults and patients with decreased pulmonary reserve. 

TableD. Reversal of Benzodiazepine Sedative Effects/Overdose 

Drug

Dosing

Onset

Peak

Duration

Comments

Flumazil(Romazicon)

 

0.2 mg over 15 sec.

After waiting 45 sec, an additional dose of 0.2 mg can be given. May repeat at 60 sec intervals up to 1 mg

30-60 sec 6-10 min 30-60 min. Duration of most benzodiazepines greatly exceeds duration of flumazenil, therefore, monitor for resedation. No more than 3 mg is recommended to be given in any 1 hour period

Administration of flumazenil will result in rapid reversal of CNS effects by competitive interaction at the benzodiazepine receptor site. Monitoring for resedation by the longer acting benzodiazepine should continue for at least 2 hours after the administration of flumazenil or until the patient returns to his/her pre-procedure baseline status, whichever is longer. 

It is important to remember that flumazenil does NOT antagonize the effects of opioids; it will not reverse respiratory depression and loss of consciousness caused by the administration of opioids.