Emergency Sedation and Analgesia: Agents and Dosing

Emergency sedation and analgesia is one of the most demanding pharmacological tasks in the prehospital and in-hospital emergency setting. Whether dealing with entrapped trauma patients, agitated emergencies, or painful procedures in the emergency department – the safe selection, dosing, and monitoring of sedatives and analgesics determines patient safety and outcome. This article provides you with a structured overview of the most common agents, their dosing, onset times, antagonists, and the relevant special considerations in pediatric patients.

Fundamental Principles of Emergency Sedation and Analgesia

Before you reach for the syringe, several fundamental considerations must be addressed:

• Clearly define the indication: Is this pure analgesia, pure anxiolysis/sedation, or procedural sedation with analgesia (PSA)?
• Prepare for airway management: Any sedation can lead to airway obstruction or apnea. Suction, bag-mask ventilation, supraglottic airway devices, and intubation equipment must be readily available.
• Establish monitoring: SpO₂, etCO₂ (if available), ECG, non-invasive blood pressure monitoring, and clinical observation are mandatory.
• Titrate rather than bolus: In most situations, the rule is: titrate slowly, wait for effect, re-dose. Exceptions are Rapid Sequence Induction (RSI) and acute agitation with danger to self or others.
• Have antagonists ready: Naloxone and flumazenil must be immediately available.

The American Society of Anesthesiologists (ASA) distinguishes four levels of sedation depth – from minimal sedation (anxiolysis) through moderate and deep sedation to general anesthesia. The transitions are fluid, and especially in the emergency setting, the risk of unintentional progression to a deeper level of sedation is real.

Opioids – Analgesia at the Core

Opioids remain the gold standard for the treatment of severe acute pain in the emergency setting. The most relevant agents are fentanyl, morphine, and sufentanil.

Fentanyl

Fentanyl is the most commonly used opioid in emergency medicine due to its rapid onset and hemodynamic stability.

• Onset IV: 1–2 minutes
• Duration of action: 30–60 minutes
• Dosing adults: 0.5–1 µg/kg IV, titrated in 25–50 µg increments
• Dosing children: 1–2 µg/kg IV, titrated
• Intranasal administration: 1.5–2 µg/kg (maximum single dose per nostril: approximately 150 µg when using a MAD – Mucosal Atomization Device)
• Special considerations: Chest wall rigidity with rapid high-dose administration (> 5 µg/kg as bolus), minimal histamine release, minimal hemodynamic effects

Morphine

Morphine is the classic opioid but has lost importance in the emergency setting due to its slower onset and histamine release.

• Onset IV: 5–10 minutes
• Duration of action: 3–4 hours
• Dosing adults: 0.05–0.1 mg/kg IV, titrated in 2–4 mg increments
• Dosing children: 0.05–0.1 mg/kg IV
• Special considerations: Histamine release with possible hypotension and bronchospasm, active metabolite (morphine-6-glucuronide) accumulates in renal insufficiency

Sufentanil

Sufentanil is primarily used in anesthesia and in emergency medical services for severely injured patients.

• Onset IV: 1–3 minutes
• Duration of action: 20–45 minutes
• Dosing adults: 0.1–0.3 µg/kg IV
• Dosing children: 0.1–0.2 µg/kg IV
• Intranasal administration: 0.5–1 µg/kg
• Special considerations: 7–10 times more potent than fentanyl, pronounced respiratory depression, excellent hemodynamic stability

Opioid Antagonist: Naloxone

• Dosing adults: 0.04–0.4 mg IV, titrated in 0.04 mg increments (start low in pure respiratory depression to avoid pain recurrence and sympathetic surge)
• Dosing children: 0.01 mg/kg IV (maximum 2 mg)
• Onset: 1–2 minutes IV
• Duration of action: 30–45 minutes – Caution: Shorter than most opioids! Re-sedation and recurrent respiratory depression are common. Consider re-dosing or continuous infusion.

Benzodiazepines – Sedation and Anxiolysis

Benzodiazepines have anxiolytic, sedative, anticonvulsant, and muscle relaxant properties. In the emergency setting, midazolam and diazepam are the most relevant agents.

Midazolam

Midazolam is the benzodiazepine of choice in the emergency setting – water-soluble, short-acting, and available via multiple routes of administration.

• Onset IV: 1–3 minutes
• Onset intranasal/buccal: 5–10 minutes
• Duration of action: 30–60 minutes (longer at higher doses)
• Dosing adults (sedation): 0.02–0.05 mg/kg IV, titrated in 1 mg increments (maximum single dose 2.5 mg, then wait for effect)
• Dosing children (sedation): 0.05–0.1 mg/kg IV
• Dosing intranasal (children, seizure): 0.2 mg/kg (max. 10 mg)
• Dosing buccal (children, seizure): 0.3 mg/kg
• Special considerations: Reduce dose by 50% in elderly patients. Synergistic respiratory depression with opioids! In case of paradoxical reaction (agitation instead of sedation) – particularly in children and elderly patients – consider switching agents.

Diazepam

• Onset IV: 2–5 minutes
• Duration of action: 1–6 hours (active metabolites up to 100 hours!)
• Dosing adults: 0.1–0.2 mg/kg IV
• Dosing children (status epilepticus, rectal): 0.5 mg/kg rectally (max. 10 mg)
• Special considerations: Long and poorly controllable duration of action due to active metabolites. Venous irritation with IV administration. Increasingly replaced by midazolam in the emergency setting.

Benzodiazepine Antagonist: Flumazenil

• Dosing adults: 0.2 mg IV, if needed re-dose 0.1 mg every 60 seconds (maximum total dose 1 mg)
• Dosing children: 0.01 mg/kg IV (max. 0.2 mg per single dose)
• Onset: 1–2 minutes
• Duration of action: 45–90 minutes
• Caution: In chronic benzodiazepine use or mixed intoxication with proconvulsant substances (e.g., tricyclic antidepressants), flumazenil can trigger seizures! The indication in the emergency setting should therefore be strictly evaluated.

Ketamine – The Multitool

Ketamine holds a unique position: it provides analgesia, sedation, and amnesia while largely preserving protective reflexes and spontaneous breathing. Its sympathomimetic effect ensures hemodynamic stability – a decisive advantage in trauma and shock.

Ketamine and Esketamine

Esketamine (S-ketamine) is the S-enantiomer of the racemate, with twice the potency. In Austria and Germany, esketamine is predominantly used. All following dose recommendations refer to esketamine – when using racemic ketamine, double the dose.

Analgesia (sub-anesthetic dosing):

• 0.125–0.25 mg/kg IV as bolus
• Alternatively: 0.1–0.3 mg/kg/h as continuous infusion
• Intranasal: 0.5–1 mg/kg

Procedural sedation:

• 0.25–0.5 mg/kg IV, titrated
• IM (if no IV access): 2–3 mg/kg

Induction of anesthesia (RSI):

• 0.5–1 mg/kg IV (esketamine)
• 1–2 mg/kg IV (racemate)

Dosing children:

• Analgesia: 0.125–0.25 mg/kg IV
• Procedural sedation: 0.5–1 mg/kg IV or 2–4 mg/kg IM (esketamine)
• Onset IV: 30–60 seconds
• Onset IM: 3–5 minutes
• Duration of action: 10–20 minutes (IV), 20–45 minutes (IM)

Special considerations:

• Psychomimetic side effects (nightmares, emergence reactions) – prophylaxis with low-dose midazolam (0.01–0.03 mg/kg IV) is common in adults, less necessary in children
• Increased salivation – prepare for suctioning, consider atropine 0.01 mg/kg IV
• Relative contraindication in poorly controlled hypertension and (controversial) elevated intracranial pressure in non-intubated patients
• Bronchodilatory effect – advantageous in status asthmaticus
• No classic antagonist available

Propofol – Procedural Sedation in the Emergency Department

Propofol offers the advantage of an extremely rapid onset and a very short duration of action. It is the standard for procedural sedation in the emergency department (e.g., cardioversion, reduction of dislocations).

• Onset IV: 15–30 seconds
• Duration of action: 5–10 minutes
• Dosing adults (PSA): 0.5–1 mg/kg IV as initial bolus, then 0.25–0.5 mg/kg every 3–5 minutes as needed
• Dosing children: 1–2 mg/kg IV (children often require higher weight-based doses)
• Special considerations: Pronounced respiratory depression and apnea, especially with rapid injection. Dose-dependent hypotension due to vasodilation and negative inotropy. Injection pain (reduced by adding lidocaine: 20–40 mg lidocaine per 200 mg propofol or prior injection with venous occlusion). No analgesic effect – combination with an opioid or ketamine is required for painful procedures.
• Contraindications: Soy and peanut allergy (with lipid-based formulation), hemodynamic instability
• No specific antagonist available

Summary Table: Emergency Sedatives and Analgesics

Agent	Primary Effect	Adult Dose IV	Onset IV	Duration	Antagonist
Fentanyl	Analgesia	0.5–1 µg/kg	1–2 min	30–60 min	Naloxone
Sufentanil	Analgesia	0.1–0.3 µg/kg	1–3 min	20–45 min	Naloxone
Morphine	Analgesia	0.05–0.1 mg/kg	5–10 min	3–4 h	Naloxone
Midazolam	Sedation	0.02–0.05 mg/kg	1–3 min	30–60 min	Flumazenil
Esketamine	Analgesia/Sedation	0.125–1 mg/kg*	30–60 s	10–20 min	None
Propofol	Sedation	0.5–1 mg/kg	15–30 s	5–10 min	None

*dose-dependent: sub-anesthetic to general anesthesia

Special Considerations in Pediatric Patients

Emergency sedation and analgesia in children requires particular care:

• Weight-based dosing is mandatory. When in doubt, estimate weight using age-based formulas (e.g., Broselow tape) or ask the parents. Overdosing is the most common preventable complication.
• Children have a higher metabolic rate and require relatively higher weight-based doses for some agents (especially propofol, ketamine).
• Functional residual capacity is lower, oxygen reserve is smaller – desaturation occurs more rapidly. Preoxygenation is essential.
• Ketamine is particularly well-established in children for procedural sedation. Emergence reactions are less frequent than in adults. IM administration is a reliable alternative when IV access is not available.
• Intranasal administration (fentanyl, midazolam, esketamine) is an excellent non-invasive option in children without IV access. Use a MAD applicator and observe the maximum volume per nostril (approximately 0.3 mL in infants, 0.5–1 mL in older children).
• Fasting status: In a true emergency, fasting is not a prerequisite for necessary sedation. Aspiration risk is minimized by adequate airway preparation, not by waiting.

Combinations and Interactions

Combining sedatives and analgesics is the rule in everyday emergency practice. The following applies:

• Opioid + benzodiazepine: Synergistic respiratory depression! Use both agents at significantly reduced doses (reduce by 30–50%).
• Ketamine + propofol ("ketofol"): This combination is used for procedural sedation. Ketamine partially compensates for propofol-induced hypotension and provides analgesia. Common mixture: 1:1 (e.g., 0.5 mg/kg each). However, the evidence regarding superiority over monotherapy is heterogeneous.
• Ketamine + midazolam: Classic combination to reduce psychomimetic side effects. Administer midazolam at low dose (0.01–0.03 mg/kg IV) before or with ketamine.

Clinical Decision Points

Agent selection is guided by the clinical situation:

• Trauma with shock: Ketamine/esketamine as the analgesic and induction agent of choice (sympathomimetic effect). Avoid propofol and high opioid doses.
• Cardioversion/reduction in the emergency department: Propofol (short duration, good controllability) or ketamine. Prefer ketamine in hemodynamically unstable patients.
• Acute agitation (delirium, intoxication, psychiatric emergency): Midazolam IM (0.1–0.15 mg/kg) or ketamine IM (esketamine 2–3 mg/kg) in non-cooperative patients without IV access. Haloperidol (5–10 mg IM) as an adjunct in non-intoxication-related delirium.
• Pediatric procedural sedation: Ketamine IM or IV as the agent of choice. Alternatively, intranasal fentanyl + midazolam for minor procedures.
• Analgesia without sedation: Low-dose esketamine (0.125–0.25 mg/kg IV) or titrated fentanyl. The combination of both agents is effective and hemodynamically stable.

Documentation and Monitoring

Every emergency sedation must be documented:

• Indication and sedation goal
• Agents administered with exact doses and times
• Monitoring parameters over time (SpO₂, etCO₂, BP, HR, depth of sedation)
• Complications and their management
• Patient status at handover/discharge

Monitoring does not end with the procedure. After sedation, monitoring must continue until the patients are safely awake and protective reflexes have fully returned. Particularly with short-acting agents (e.g., naloxone, flumazenil), watch for re-sedation.

Practical Training

The safe application of emergency sedation and analgesia requires more than theoretical knowledge. Dose calculation under stress, airway management during complications, recognizing deepening sedation, and targeted intervention are best trained in realistic simulation scenarios. In the Notarzt-Refresher by Simulation Tirol, you work through these scenarios in a hands-on manner – from procedural sedation to management of the difficult airway under sedation. More information is available at simulation.tirol.