Analgesia/Sedation

Rapid Review

• Mechanism of Action: Antipyretic/Analgesic. Inhibits prostaglandin synthesis on CNS and has direct action on hypothalamic heat-regulating systems.
• Indications: Mild-moderate pain; fever
• Contraindications: Allergy to class/drug
• Dosage: 1000 mg PO q4-6 hours
• Onset: 15-30 minutes PO for analgesia. 30 minutes for antipyretic
• Duration: 4-6 hours
• Adverse Reactions: Nausea, rash, and headache are common. 
• Special Considerations: Doses above 4 grams/day may cause liver toxicity

Pearls

• Doses above 4,000 mg per day can cause liver toxicity. That threshold is reduced in patients with certain comorbid conditions (cirrhosis, advanced age, malnutrition, low body weight)
• Combining or alternating with NSAIDs (eg. naproxen, ibuprofen) can help reduce opiate use. 

Deep Dive

• Acetaminophen (Drugs.com)

Rapid Review

• Mechanism of Action: Benzodiazepine; enhances inhibitory effects of GABA receptors
• Indications: Seizure abortion, agitation, alcohol withdrawal, muscle spasm
• Contraindications: Allergy to drug/class, severe hepatic impairment
• Dosage: Generally 2-10 mg PO/IV/IM q 6 hrs prn
• Onset: 1-3 minutes (IV), 15-60 minutes (PO)
• Duration: 12 hours
• Adverse Reactions: Respiratory depression, sedation, hypotension, 
• Special Considerations: Pregnancy category D

Pearls

• Diazepam is often used as a rescue medication at home because it remains stable in pre-mixed liquid and is available as a rectal gel.
• Like other benzodiazepines, there is a small chance of rare paradoxical reactions (rage, hostility, aggression). Keep this in mind, especially if using this for acute agitation. 

Deep Dive

• Diazepam (PubMed)

Rapid Review

• Mechanism of Action: Ultrashort-acting non-barbiturate hypnotic. Exhibits GABA-like effects on brain stem reticular formation.
• Indications: RSI induction
• Contraindications: Allergy to drug/class
• Dosage: 0.3mg/kg IV
• Onset: 30-60 seconds
• Duration: 3-5 minutes
• Adverse Reactions: Adrenal suppression, lowers seizure threshold
• Special Considerations: Etomidate does not provide any analgesic effect.
• Etomidate is a commonly used sedative agent used for induction for intubation. It has a rapid onset with little effect of hemodynamics, making it a valuable agent especially in critically ill or hypotensive patients.

Pearls

• Etomidate has a rapid onset and a short duration of action, making it ideal for cardioversion.
• Approximately 30% of all patients recieiving etomidate will experience myoclonus. This makes it a less than ideal sedative for orthopedic procedures. 

Deep Dive

• The EvK Trial: Ketamine vs Etomidate for RSI (REBEL EM)

Rapid Review

• Mechanism of Action: Narcotic opiate analgesic; binds to opiate receptors and blocks ascending pain pathways.
• Indications: Moderate-severe pain, adjunct to sedation
• Contraindications: Allergy to class/drug, respiratory depression, paralytic ileus
• Dosage: Generally 1-2 mcg/kg IV/IM q30-60 minutes prn
• Onset: 1-2 minutes (IV)
• Duration: 2-4 hours
• Adverse Reactions: Apnea, confusion, constipation, nausea/vomiting
• Special Considerations: None

Pearls

• Fentanyl tends to have fewer side effects, such as hypotension and respiratory depression, than other opiates. On rare occassions though, it may cause “wooden chest syndrome”, which is a pathologic chest wall rigidity that usually follows high or rapid doses of fentanyl. 
• Fentanyl has a shorter duration of action compared to other opiates, making it ideal as an analgesic adjunct for procedures. However, for ongoing pain management, consider longer-acting opiates like hydromorphone or morphine. 

Deep Dive

• Association between fentanyl treatment for acute pain in the ED and opioid use two weeks after discharge (American Journal of Emergency Medicine)

Rapid Review

• Mechanism of Action: Opioid agonist; pure opioid that binds to several opioid receptors, acting on the mu-opioid receptors to produce analgesia and sedative effects
• Indications: Moderate-severe pain
• Contraindications:  Hypersensitivity, respiratory depression, GI obstruction/ileus, hypotension
• Dosage: 1-2 mg IV q 3-6 hours
• Onset: <5 minutes (IV),  15-30 minutes (PO)
• Duration: 2-3 hours (IV), 3-4 hours (PO)
• Adverse Reactions: Hypotension, respiratory depression, pruritus, nausea/vomiting
• Special Considerations: 1 mg of IV Dilaudid equals approximately 7 mg of morphine

Pearls

• Hydromorphone has fewer side effects (e.g. pruritus, hypotension) compared to morphine, but has higher rates of euphoria and greater potential for abuse.
• 1 mg hydromorphone = 7 mg morphine = 70 mcg fentanyl

Deep Dive

• Hydromorphone (PubMed)

Rapid Review

• Mechanism of Action: NSAID; inhibits OX-1 and COX-2 enzymes to decrease expression of prostaglandin precursors, thus producing analgesic, antipyretic, and anti-inflammatory effects.
• Indications: Mild-moderate pain, fever, 
• Contraindications: Known hypersensitivity, active bleeding
• Dosage: Generally 800 mg PO q8 hours
• Onset: 30 minutes
• Duration: 6 hours
• Adverse Reactions: GI bleeding, nephrotoxicity, SJS, dyspepsia, nausea, dizziness
• Special Considerations: None

Pearls

• Ibuprofen has been shown to have an analgesic ceiling effect at 400 mg for most causes of pain in the ED. Prescribing above this dose will not improve pain, but will increase adverse effects.
• Avoid giving Ibuprofen when possible in patients with kidney or heart disease due to the risk of cardiac/renal complications. 

Deep Dive

• Comparing of Oral Ibuprofen at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department (PubMed)

Rapid Review

• Mechanism of Action: NMDA receptor antagonist; dissociative anesthetic; analgesic/sedative; 
• Indications: Analgesia, sedation, RSI induction
• Contraindications: Allergy to drug/class
• Dosage:
  • Analgesic dose: 0.1-0.5 mg/kg IV
  • Procedural sedation dose: 0.5-1 mg/kg IV 
  • RSI induction: 2 mg/kg IV
  • Combative patient: 4-6 mg/kg IM or 1 mg/kg IV
• Onset: Less than 1 minute (IV); 4 minutes (IM)
• Duration: 5-15 minutes (IV); 15-30 minutes (IM)
• Adverse Reactions: Laryngospasm, apnea, hypersalivation
• Special Considerations: Does not affect respiratory drive, making it useful for awake or fiberoptic intubations. Ketamine is first line as an induction agent for intubations in asthmatic patients due to it’s bronchodilatory effects.

Pearls

• Ketamine is advantageous for hemodynamically unstable patients compared to other analgesics/sedatives (Ex. opiates, propofol), as it does not cause hypotension.
• Due to it’s bronchodilatory effects, ketamine is the preferred induction agent for RSI in asthma/COPD patients.

Deep Dive

• Update from the K-Hole: Ketamine in the ED (EM Ottawa)

Rapid Review

• Mechanism of Action: Benzodiazepine; enhances inhibitory effects at GABA receptors. 
• Indications: Seizures, agitation, delirium tremens, serotonin syndrome.
• Contraindications:
• Dosage: 1-2 mg IV bolus; 1-10 mg/hr infusion
• Onset: 5 minutes (IV); 15-30 minutes (IM)
• Duration: 6-8 hours
• Adverse Reactions: Respiratory depression, hypotension, ataxia
• Special Considerations: None

Pearls

• Lorazepam has a slower onset of action than midazolam or diazepam, but longer duration. It has comparable efficacy for seizures when given IV, but is not the preferred agent of choice if administered via alternative routes (intranasal, intramuscular, rectal, etc.).
• Like other benzodiazepines, it can cause significant respiratory depression when paired with opiates. Given the extended duration of lorazepam, there is an increased risk of therapeutic overlap. 

Deep Dive

• Parenteral Benzodiazepines (Core EM)

Rapid Review

• Mechanism of Action: Benzodiazepine; occupies GABA receptors to cause membrane hyperpolarization and neuronal inhibition. Produces sedation, anxiolysis, anterograde amnesia, and anticonvulsant effects.
• Indications: Acute seizure, procedural sedation, agitation, RSI induction (not first line)
• Contraindications: Hypersensitivity, hypotension, acute angle-closure glaucoma
• Dosage:
  • Agitation: 1-5 mg IV/IM
  • Procedural sedation: 0.05 mg/kg IV
  • Seizure: 10 mg IV/IM
• Onset: 1-7 minutes (IV)
• Duration: < 2 hours
• Adverse Reactions: Respiratory depression, hypotension, drowsiness, nausea/vomiting
• Special Considerations: Also available intranasally

Pearls

• Midazolam is ideal for seizure management given it’s rapid onset and it’s ability to be given multiple routes (IV, IM, IN, Buccal). 
• 2 mg midazolam = 1 mg lorazepam = 8 mg diazepam.

Deep Dive

• Midazolam (PubMed)

Rapid Review

• Mechanism of Action: Opiate analgesic; binds to opioid receptors in the CNS to inhibit ascending pain pathways. Alters patient’s perception and response to pain.
• Indications: Acute moderate-severe pain
• Contraindications: Allergy to drug/class, severe asthma, paralytic ileus
• Dosage: 0.1 mg/kg bolus (IV)
• Onset: 5 minutes, peak at 20 minutes
• Duration: 4-5 hours
• Adverse Reactions: Respiratory depression, hypotension, nausea/vomiting, urticaria, dependence
• Special Considerations: None

Pearls

• Due to it’s histamine release, morphine tends to cause more side effects (pruritus, hypotension) than fentanyl
• 4 mg morphine = 40 mcg fentanyl = 0.5 mg hydromorphone

Deep Dive

• The Death of MONA in ACS – Morphine (REBEL EM)

Rapid Review

• Mechanism of Action: General anesthetic; Short acting, lipophilic sedative/hypnotic agent that causes global CNS depression, presumably through agonist activity on GABAa receptors and sodium channel blockade.
• Indications: Procedural sedation, status epilepticus
• Contraindications: Hypersensitivity, severe hypotension
• Dosage:
  • Procedural sedation: 1 mg/kg IV bolus, then 0.5 mg/kg q3 minutes
  • RSI induction: 1.5 mg/kg IV bolus
  • Ventilator sedation: 5-50 mcg/kg/min IV, increase 5 mcg/kg/min q10 minutes prn
• Onset: 30-45 seconds
• Duration: 3-10 minutes
• Adverse Reactions: Paint at injection site, hypotension, myoclonus, propofol infusion syndrome (PRIS)
• Special Considerations: None

Pearls

• Propofol has an extremely fast onset and short duration, making it the preferred agent for patients requiring frequent neurological assessments.
• Propofol has no analgesic effects. When it for procedural sedation, It must be co-administered with an analgesic (ex. ketamine, fentanyl, morphine).

Deep Dive

• Propofol (PubMed)