Medications During Resuscitation: Dosages and Timing

Pharmacological therapy during resuscitation is a central component of Advanced Cardiac Life Support (ACLS). At the same time, it must never delay or overshadow basic measures – high-quality chest compressions and early defibrillation. However, the right drug, at the right time, in the right dose, and via the right route of administration can make the decisive difference. This article provides you with a systematic overview of the most important resuscitation medications for adults and children, based on the current AHA guidelines.

Basic Principles of Medication Administration During Resuscitation

Before you draw up any medication, some fundamental rules must be internalized:

• Chest compressions have absolute priority. Medication administration must not compromise CPR quality. Interruptions of chest compressions for drug administration should be kept to an absolute minimum.
• Intravenous (IV) is the preferred access route. A peripheral venous access is standard. If this cannot be established quickly, the intraosseous (IO) route is an equivalent alternative.
• Endotracheal administration is no longer routinely recommended by the AHA and should only be considered as an absolute last resort when neither IV nor IO access is available.
• Flush after every medication administration: With peripheral venous administration, flush with 20 ml of 0.9% NaCl as a bolus and briefly elevate the extremity to accelerate transport to the central circulation. Use a flush with IO administration as well.
• Rhythm analysis determines the algorithm: Medication selection is primarily guided by the presenting cardiac rhythm – shockable (ventricular fibrillation/VF, pulseless ventricular tachycardia/pVT) versus non-shockable (asystole, pulseless electrical activity/PEA).

Epinephrine (Adrenaline) – The Central Resuscitation Drug

Epinephrine is the most important and best-studied medication in the cardiac arrest setting. Its effect is primarily based on α1-adrenergic vasoconstriction, which increases coronary and cerebral perfusion pressure during CPR. The β-adrenergic component increases myocardial contractility but can also increase myocardial oxygen consumption and promote arrhythmias.

Adult Dosing

• Standard dose: 1 mg IV/IO as a bolus
• Repeat: every 3–5 minutes throughout CPR
• Concentration: typically 1:10,000 (0.1 mg/ml) for IV administration; the 1:1,000 (1 mg/ml) ampoule must be diluted accordingly or given undiluted with a flush

Timing by Rhythm

The timing of the first epinephrine dose differs fundamentally depending on the rhythm:

• Non-shockable rhythms (asystole, PEA): Administer epinephrine as early as possible – ideally as soon as IV/IO access is established. Studies show that early epinephrine administration in non-shockable rhythms is associated with a higher rate of ROSC (Return of Spontaneous Circulation).
• Shockable rhythms (VF/pVT): Administer epinephrine only after the second unsuccessful shock, typically during the third CPR cycle. The rationale: In VF/pVT, defibrillation is the causal therapy. Too early administration of epinephrine could theoretically increase the defibrillation threshold.

Pediatric Dosing (PALS)

• Standard dose: 0.01 mg/kg IV/IO (equivalent to 0.1 ml/kg of the 1:10,000 solution)
• Maximum single dose: 1 mg
• Repeat: every 3–5 minutes
• High-dose epinephrine (0.1 mg/kg) is not recommended based on current evidence, as no survival benefit has been demonstrated

Clinical Pitfalls

• Risk of confusion between 1:1,000 and 1:10,000 – a classic, potentially lethal medication error. Always read back the concentration out loud within the team.
• Epinephrine is light-sensitive and thermolabile – check storage conditions.
• After ROSC, an inadvertently excessive epinephrine dose can trigger a hypertensive crisis or tachyarrhythmia.

Amiodarone – Antiarrhythmic for Shock-Refractory VF/pVT

Amiodarone is the first-line antiarrhythmic for shock-refractory ventricular fibrillation and pulseless ventricular tachycardia. It acts through blockade of potassium, sodium, and calcium channels as well as through anti-adrenergic properties.

Adult Dosing

• First dose: 300 mg IV/IO as a bolus (after the third unsuccessful shock, typically given simultaneously with the first epinephrine dose)
• Second dose: 150 mg IV/IO as a bolus if VF/pVT persists
• Administration: can be given undiluted as a bolus; no slow infusion is necessary in the resuscitation setting

Pediatric Dosing (PALS)

• First dose: 5 mg/kg IV/IO as a bolus
• Second dose: 5 mg/kg IV/IO, can be repeated
• Maximum single dose: 300 mg

Lidocaine as an Alternative

Lidocaine (1–1.5 mg/kg IV in adults, then 0.5–0.75 mg/kg every 5–10 minutes, maximum dose 3 mg/kg) can be used as an alternative to amiodarone for shock-refractory VF/pVT when amiodarone is not available. The AHA guidelines consider both medications largely equivalent, although amiodarone is preferred in most centers.

Atropine – Role and Limitations

Atropine as a parasympatholytic agent blocks the influence of the vagus nerve on the sinus node and AV node. Its role in resuscitation has changed significantly in recent guideline revisions.

Important: No Longer Recommended in Cardiac Arrest

The AHA no longer routinely recommends atropine for asystole or PEA. Studies have shown no survival benefit. Atropine has therefore been removed from the ACLS cardiac arrest algorithm.

Indication: Symptomatic Bradycardia (Peri-Arrest)

• Adult dosing: 0.5 mg IV every 3–5 minutes
• Maximum dose: 3 mg (equivalent to complete vagal blockade)
• Caution: Doses below 0.5 mg can paradoxically worsen bradycardia (paradoxical vagotonic effect)

Pediatric Dosing

• 0.02 mg/kg IV/IO
• Minimum dose: 0.1 mg (to avoid paradoxical bradycardia)
• Maximum single dose: 0.5 mg (child), 1 mg (adolescent)

Sodium Bicarbonate – Targeted Use for Specific Indications

Sodium bicarbonate is not a routine medication in resuscitation. Blind buffering without blood gas analysis can cause more harm than good: the resulting CO₂ load can paradoxically worsen intracellular acidosis, shift the oxygen dissociation curve to the left, and cause hypernatremia and hyperosmolarity.

Indications

• Pre-existing metabolic acidosis (e.g., in chronic renal insufficiency)
• Hyperkalemia as a suspected or confirmed cause of cardiac arrest
• Tricyclic antidepressant (TCA) intoxication – here sodium bicarbonate is the specific therapy, as alkalinization antagonizes the sodium channel blockade
• Prolonged resuscitation when severe acidosis (pH < 7.1) is documented

Adult Dosing

• 1 mEq/kg IV as an initial dose (approximately 1 ml/kg of the 8.4% solution)
• Titrate further doses based on blood gas analysis
• Do not mix with other medications through the same access – be aware of incompatibilities (especially with epinephrine and calcium)

Pediatric Dosing

• 1 mEq/kg IV/IO
• In neonates: prefer the 4.2% solution (half osmolarity)

Calcium – Only with a Clear Indication

Calcium is not part of routine therapy in cardiac arrest. Indiscriminate administration can worsen ischemic cell damage through intracellular calcium overload.

Indications

• Hyperkalemia – calcium stabilizes the myocardial membrane without lowering the potassium level
• Hypocalcemia – e.g., in massive transfusion (citrate toxicity), chronic renal insufficiency
• Hypermagnesemia
• Calcium channel blocker intoxication

Adult Dosing

• Calcium chloride 10%: 10–20 ml (equivalent to 1–2 g or 6.8–13.6 mmol Ca²⁺) slow IV
• Calcium gluconate 10%: 30 ml IV (contains less elemental calcium than calcium chloride)
• Calcium chloride is preferred, as it delivers three times more ionized calcium than calcium gluconate at the same volume
• Caution: Calcium chloride is highly irritating to veins – avoid extravasation with peripheral venous administration. IO administration is possible.

Pediatric Dosing

• Calcium chloride 10%: 20 mg/kg IV/IO (0.2 ml/kg), slowly over 10–20 seconds
• Maximum single dose: 2 g

Magnesium – Specific Indication for Torsades de Pointes

Magnesium is the drug of choice for Torsades de Pointes (polymorphic ventricular tachycardia with prolonged QT interval) and should be given without delay in this situation.

Adult Dosing

• 1–2 g magnesium sulfate IV/IO as a bolus over 1–2 minutes for pulseless Torsades de Pointes
• For Torsades de Pointes with a pulse: infuse 1–2 g over 15 minutes
• For documented hypomagnesemia in cardiac arrest: 1–2 g IV/IO

Pediatric Dosing

• 25–50 mg/kg IV/IO (maximum dose 2 g)
• Bolus for pulseless arrest, slow infusion when circulation is maintained

Clinical Note

In VF/pVT that does not respond to defibrillation, epinephrine, and amiodarone, you should always consider hypomagnesemia in your differential diagnosis – especially in patients on diuretic therapy, with chronic alcohol abuse, or malnutrition.

Summary Overview: Timing in the ACLS Algorithm

For better orientation in the time-critical setting, here is how medications fit into the algorithm for adults:

Shockable Rhythm (VF/pVT)

1. 1st shock → immediate CPR for 2 minutes
2. 2nd shock → immediate CPR for 2 minutes
3. 3rd shock → Epinephrine 1 mg IV/IO + Amiodarone 300 mg IV/IO → CPR for 2 minutes
4. 4th shock → Epinephrine 1 mg IV/IO (if 3–5 minutes since last dose) → CPR for 2 minutes
5. 5th shock → Amiodarone 150 mg IV/IO (second dose) → CPR for 2 minutes
6. Further cycles: continue epinephrine 1 mg every 3–5 minutes

Non-Shockable Rhythm (Asystole/PEA)

1. Start CPR → Epinephrine 1 mg IV/IO as early as possible
2. Rhythm check every 2 minutes
3. Continue epinephrine 1 mg every 3–5 minutes
4. Systematically search for and treat reversible causes (Hs and Ts)

Reversible Causes – The Hs and Ts

Medication selection is significantly determined by the underlying cause of cardiac arrest. Systematically working through the Hs and Ts is essential:

Hs:

• Hypovolemia → volume bolus
• Hypoxia → airway management, oxygenation
• Hydrogen ions (acidosis) → consider sodium bicarbonate
• Hypo-/hyperkalemia → calcium, sodium bicarbonate, insulin/glucose
• Hypothermia → rewarming

Ts:

• Thrombosis (coronary) → consider PCI
• Thrombosis (pulmonary) → consider thrombolysis
• Tamponade (pericardial) → pericardiocentesis
• Toxins → specific antidotes
• Tension pneumothorax → needle decompression

Special Situations

Tricyclic Antidepressant Intoxication

Sodium bicarbonate is the key therapy here: 1–2 mEq/kg IV as a bolus, target pH 7.45–7.55. Repeat as needed. Alkalinization reduces the free drug concentration and antagonizes the sodium channel blockade.

Hyperkalemia-Induced Cardiac Arrest

Therapy cascade:

1. Calcium chloride 10%: 10–20 ml IV (membrane stabilization)
2. Sodium bicarbonate: 50 mEq IV (intracellular potassium shift)
3. Insulin 10 units + glucose 25 g IV (intracellular potassium shift)
4. Plan hemodialysis as definitive therapy

Local Anesthetic Systemic Toxicity (LAST)

In cardiac arrest due to systemic local anesthetic toxicity:

• Lipid emulsion 20% (Intralipid): 1.5 ml/kg IV as a bolus, followed by 0.25 ml/kg/min as an infusion
• Bolus can be repeated 1–2 times if needed
• Maximum dose: 12 ml/kg in the first 30 minutes

Documentation and Team Communication

In the resuscitation setting, clear documentation of administered medications including timing is essential. The AHA recommends a dedicated person for record-keeping. Use closed-loop communication:

• Order: "Please give 1 mg epinephrine intravenously."
• Read-back: "1 mg epinephrine intravenously is being prepared."
• Confirmation: "1 mg epinephrine intravenously has been given, time noted."

This approach reduces medication errors and ensures correct dosing intervals.

Practical Training

The safe use of resuscitation medications requires more than theoretical knowledge. Dosages, timing, and routes of administration must be retrievable under realistic stress – and the entire team must work together seamlessly. In the ACLS course from Simulation Tirol, you train exactly these scenarios: megacode simulations with real medication decisions, rhythm-driven algorithms, and structured team management. This is how knowledge becomes confident action when it matters most.