Sedation of Intensive Care Patients English

Sedation of Intensive Care Patients

Sedation for intensive care patients is provided according to the patient’s need for anxiety relief and pain management and is tailored to ongoing medical treatments and interventions. Sedation is usually given as an intravenous continuous infusion of two separate drugs in parallel. Sedation is routinely provided to patients who are on ventilators to tolerate the tube and synchronize with ventilator breathing. An oral tube is very difficult to tolerate without sedation. A tracheal cannula is less irritating than a nasal tube, which is less irritating than an orally placed tube.

Common drugs given to patients on ventilators include propofol plus remifentanil or propofol plus fentanyl in continuous infusion. Sedation can also be administered as an inhalant via a ventilator or as intermittent bolus doses. Continuous infusions are primarily given to patients on ventilators, while non-ventilated patients usually receive intermittent doses of medications, such as morphine.

Sedation should allow for mobilization, even of intubated patients, and is always adjusted according to the need for pain relief and circadian rhythm. The goal is to enable the patient to be awake, mobilized, and pain-free with a normal circadian rhythm and functioning natural processes.

Drugs and sedation depth are administered with regard to:

• Alertness (grading according to MAAS, SAS, or RASS)
• Pain
• Anxiety, possible delirium
• Patient comfort
• Mobilization
• Ventilator treatment and breathing ability
• Surgical wounds, drains, catheters, tubes, IV lines, etc.
• Minimal circulatory and respiratory stress
• Nursing needs, wound care
• Natural functions, gastrointestinal and renal function – diuresis
• Circulation and circulatory impact
• Intracranial pressure – ICP
• Circadian rhythm
• “WUC” – wake up call
• Awakening and extubation

Patient comfort during different levels of sedation is still relatively unknown. New research suggests that patients who clearly remember their intensive care experience have fewer unpleasant memories (hallucinations, nightmares, paranoid delusions) than those with poorer recollections. The RACHEL study found that patients who were deeply sedated for extended periods were more affected by hallucinations and nightmares. Sedation is individually adjusted based on the patient’s condition and need for comfort, care, and mobilization potential.

A desired sedation level (MAAS or RASS level) should be established daily for each patient after discussions with the care team. Most commonly, MAAS 2 or 3. The doctor prescribes the appropriate MAAS level, e.g., 2. If the patient is then noted to correspond to MAAS 1, the nurse adjusts the sedative medication until the patient is back at MAAS 2, after which the sedation is restarted at a lower rate than before.

Before awakening and extubation, it is common to reduce (or pause) the propofol infusion while maintaining a low dose of opioid to allow for awakening without excessive discomfort. It is generally possible to extubate with a continued infusion of low-dose fentanyl or remifentanil. Abrupt cessation of remifentanil can lead to too rapid awakening with pain and high stress during extubation. Additionally, abrupt awakening can make it difficult to assess the patient’s ability to breathe independently. Before remifentanil is discontinued at extubation, it may be appropriate to give, for example, 5-10 mg of morphine or oxycodone intravenously. Before extubation, the patient should be able to look up, make eye contact, and breathe calmly on their own.

Sedation of Patients on Ventilators

Pharmacokinetics of Sedative ICU Drugs

Goal-Oriented Sedation

Different MAAS or RASS levels are required for different patients. Increased sedation (low score) can increase the risk of respiratory and circulatory complications, while patient safety sometimes necessitates it.

A desired RASS level should be established daily for each patient after discussions with the care team. Most commonly, RASS 0 or −1. The doctor prescribes the appropriate RASS, e.g., −1. If the patient is then noted to correspond to RASS −3, the nurse stops the sedative medication until the patient returns to RASS −2, after which the sedation is restarted at a lower rate than before.

Sedatives & Analgesics – Summary

Dexmedetomidine

• Indication: Sedation during ventilator treatment
• Dosage: If hemodynamically stable, a bolus dose of 1 μg/kg can be given over 10 minutes.
• Maintenance infusion: 0.2-1.4 μg/kg/h. A suitable starting dose is around 0.7 μg/kg/h for sedation.
• Contraindications: AV block II-III, pregnancy, significant hypovolemia. Combination with clonidine.
• α1-α2 agonist 1:1620
• t_1⁄2 = 2 h
• Drug name: Dexdor^®
• Injection solution: 8 μg/ml iv

Fentanyl

• Indication: Sedation during ventilator treatment
• Maintenance dose for sedation in ICU:
  • Adults: 0.5-2 μg/kg/h
  • Children: 0.5-1 μg/kg/h
• Standard dose: 0.5 μg/kg/h
• Drug name: Fentanyl^®, Leptanal^®
• Solution: 50 μg/ml iv

Haloperidol (Haldol)

• Indication: Severe agitation, confusion
• Dosage: 1-5 mg iv bolus, 2.5-5 mg x 4 can be tried. Dose reduction in liver failure.
• Low-dose neuroleptic, dopamine blocker
• t_1⁄2 = 19 h
• Caution: Parkinson’s disease, long QT syndrome, hypokalemia, extrapyramidal side effects.
• Drug name: Haldol^®
• Solution: Injection solution 5 mg/ml. Tablet 1 mg.

Clonidine

• Indication: Sedation during ventilator treatment, treatment of stress and agitation
• Dosage: Continuous infusion: 2-5 ml/h, 0.25-1 μg/kg/h. Usual dose 0.33 μg/kg/h or injection 75-150 μg x 4 iv. Same dose orally.
• Max dose in continuous infusion: 2 μg/kg/h.
• α1-α2 1:200 agonist, parenteral = oral dose
• t_1⁄2 = 8 h – longer in continuous infusion
• Contraindications: Bradycardia, SSS, AV block II-III, combination with dexmedetomidine, severe hypotension
• Drug name: Catapresan^®
• Injection solution 150 μg/ml. For continuous infusion 15 μg/ml.

Midazolam

• Indication: Sedation during ventilator treatment. Seizure treatment.
• Effect within 2 min – maximum effect at 5-10 min
• Dosage: Adult bolus 0.5-1-2 mg iv
• Infusion: 0.1-0.3 mg/kg/h, 1-25 mg/h
• Intramuscular: 5-10 mg (5 mg/ml)
• Children’s bolus: 0.05-0.1 mg/kg
• Drug name: Midazolam^®, Dormicum^®
• Solution: 1 mg/ml, 5 mg/ml iv

Propiomazine (Propavan)

• Indication: Sleep, sleeping pill
• Dosage: 1-2 tablets no later than 20:00. Note: Significant “hang-over” effect
• t_1⁄2 = 8 h
• Drug name: Propavan^®
• Strength: Tablet 25 mg

Propofol

• Indication: Sedation during ventilator treatment, induction of anesthesia
• Dosage: 0.1-4 mg/kg/h
• Drug names: Diprivan^®, Propolipid^®, Profast^®, Propofol-Lipuro^®
• Injection solution: 10 mg/ml or 20 mg/ml iv

Remifentanil

• Indication: Sedation during ventilator treatment, analgesia
• Dosage: 0.025-0.25 μg/kg/min. For painful procedures: 0.25 – max 0.75 μg/kg/h
• Drug names: Remifentanil^®, Ultiva^®
• Injection solution: 50 μg/ml iv

Zopiclone (Imovane)

• Indication: Sleep, sleeping pill
• Dosage: 1 tablet at night, taken before 02:00. Max 15 mg.
• Drug names: Zopiclone^®, Zopiclone^®, Imovane^®
• Tablet: 5/7.5 mg

Sedatives & Analgesics for Intensive Care Patients

Alfentanil

Intravenous sedative and analgesic.

Drug name: Rapifen^®

• Dosage: 0.5-3 mg/h (1-6 ml/h) in a concentration of 0.5 mg/ml.
• Side effects: Hypotension, apnea.
• Injection solution: 0.5 mg/ml = 500 μg/ml

Alfentanil can cause respiratory failure and respiratory depression. It may lead to muscle rigidity, particularly at high doses, and difficulty in manually ventilating the patient. It can cause somnolence and increased fatigue. Bradycardia and hypotension may occur at high doses. Muscle rigidity has been observed with higher frequency at high doses and rapid administration of alfentanil. Bradycardia and possible asystole can occur if the patient is given insufficient doses of anticholinergics or if alfentanil is combined with non-vagolytic muscle relaxants.

Warning: Alfentanil reduces the need for hypnotics necessary to maintain sedation, so the dose of hypnotics should be reduced. Since the adverse hemodynamic effects of alfentanil are more pronounced and frequent in patients with ASA III-IV than with longer-acting opioids, great caution should be exercised when administering alfentanil to this patient group.

Dexmedetomidine

Sympatholytic. Central alpha₂-agonist. Provides sedation, reduced heart rate, lowered blood pressure, and less stress response. Dexmedetomidine is the S-enantiomer of medetomidine.

Drug name: Dexdor^®

• Dosage: In continuous infusion 0.2-1.4 µg/kg/h. The appropriate starting dose is approximately 0.7 µg/kg/h for sedation
• A very selective α2-adrenergic agonist
• α2:α1 ratio of about 1600:1. In comparison, clonidine has an α2:α1 ratio of about 220:1
• The most commonly reported side effects were hypotension, bradycardia, and dry mouth
• No significant respiratory depression at conventional clinical doses
• 94% protein-bound
• Onset time: 20-30 minutes (duration 4-8 hours)
• Elimination half-life: t_1/2 alpha: 6 min
• Elimination half-life: t_1/2 β: 2-3 hours
• Hepatic glucuronidation and conjugation
• Maintenance dose: Start with 1 μg/kg as a bolus dose over 10 min, then 0.2-1.4 μg/kg/hour
• Injection solution 100 µg/ml
• For continuous infusion, dilute to 4 µg/ml or 8 µg/ml.

Dosage: The infusion rate is adjusted incrementally within the dose range of 0.2 – 1.4 micrograms/kg/hour. A loading dose of Dexdor is not recommended and is associated with increased side effects. Propofol or midazolam can be given as needed until the clinical effect of Dexdor is achieved. Patients already intubated and sedated can switch to dexmedetomidine with an initial infusion rate of 0.7 micrograms/kg/hour. The infusion rate can then be adjusted incrementally within the dose range of 0.2 – 1.4 micrograms/kg/hour.

Indication: For sedation of adult intensive care patients who require a level of sedation that is not deeper than being arousable by verbal stimulation (equivalent to Richmond Agitation-Sedation Scale (RASS) 0 to -3). Sympathotonic states with hypertension, stress, withdrawal.

Concentration: One ml of concentrate contains dexmedetomidine hydrochloride equivalent to 100 micrograms of dexmedetomidine. The concentration of the infusion solution after dilution should be either 4 micrograms/ml or 8 micrograms/ml.

Side effects: Hypotension, bradycardia, respiratory failure.

Warning: Abrupt discontinuation of high doses has been associated with symptoms such as palpitations, anxiety, nervousness, motor restlessness, and in rare cases, blood pressure exceeding untreated levels.

Contraindications: Hypersensitivity to dexmedetomidine or any excipient, severe bradyarrhythmia caused by sick sinus syndrome or AV block grade II-III, hypotension.

Fentanyl

Intravenous anesthetic and analgesic. Fentanyl is a first-line agent for critically ill patients with hemodynamic instability. Fentanyl is 100-300 times more potent than morphine. It has high lipid solubility.

Drug name: Fentanyl^®, Leptanal^®

• Dosage: For sedation of intensive care patients, a typical dosage is 1-2-(4) ml fentanyl intravenously per hour. Maintenance dose: 1-2 μg/kg/h
• Initial dose: 1-2 μg/kg as a bolus
• Onset time: 5-6 minutes
• Duration of bolus dose: 0.5-1 hour
• Elimination half-life: 30-60 minutes (9-16 hours after prolonged dosing)
• Injection solution: 0.05 mg/ml = 50 μg/ml

In ventilated patients, a loading dose of fentanyl can be given as a rapid infusion of approximately 1 μg/kg/minute during the first 10 minutes followed by an infusion of approximately 0.5 μg/kg/h. Alternatively, the loading dose can be given as a bolus. The infusion rate should be titrated according to individual patient response; lower rates may be sufficient.

Fentanyl is a potent opioid and a short-acting intravenous anesthetic and analgesic. It is intended for use during anesthesia for surgical procedures and for sedation during painful or stressful medical procedures. Fentanyl is a selective and potent μ-opioid agonist with rapid onset and short duration. Despite the fast action, the maximum analgesic and respiratory-depressant effect is reached after several minutes. Normally, the analgesic effect of an intravenous injection of 100 micrograms fentanyl lasts approximately 30 minutes. In pharmacodynamic terms, fentanyl resembles morphine but has more potent analgesic and respiratory-depressant effects. Even in large bolus doses, fentanyl has often been used for induction of anesthesia in patients with heart disease due to its cardiovascular stability and ability to attenuate hemodynamic responses to intubation.

Plasma protein binding is 80-85%. Fentanyl is not plasma cell-bound, and protein binding is minimally affected by pH. It is metabolized in the liver to inactive metabolites.

Plasma concentrations of fentanyl decrease rapidly after an intravenous injection. The elimination of fentanyl is triphasic with half-lives of about 1 minute, 15 minutes, and 6 hours. The central compartment distribution volume is about 15 liters, and the total distribution volume is about 400 liters. Secondary plasma peaks may occur. About 75% of the dose is eliminated within 72 hours.

Dosage

For anesthesia procedures, the usual initial dose of fentanyl for adults is 50-100-200 μg, 1-2-4 ml, injected slowly intravenously. The dose may be repeated 20-30-45 minutes after the initial dose. Secondary respiratory depression has been observed in cases of dose accumulation. During continuous infusion, there is a risk of accumulation.

Fentanyl should be used with caution in uncompensated hypothyroidism, lung disease, particularly with reduced lung capacity, alcohol abuse, liver or kidney insufficiency. Tolerance and dependence may be induced. Fentanyl reduces the need for hypnotics necessary to maintain anesthesia, so the dose of hypnotics or volatile anesthetics should be reduced.

Maintenance dose for sedation in ICU

• Adults: 0.5-2 μg/kg/hour
• Children: 0.5-1 μg/kg/hour
• Standard dose: 0.5 μg/kg/hour

In ventilated patients, a loading dose of fentanyl can be given as a rapid infusion of approximately 1 μg/kg/minute during the first 10 minutes followed by an infusion of approximately 0.5 μg/kg/hour. Alternatively, the loading dose can be given as a bolus. The infusion rate should be titrated according to individual patient response; lower infusion rates may be sufficient.

In ventilated patients, a loading dose of fentanyl can be given as a rapid infusion of approximately 1 μg/kg/minute during the first 10 minutes followed by an infusion of approximately 0.1 μg/kg/minute. Alternatively, the loading dose can be given as a bolus. The infusion rate should be titrated according to individual patient response; lower rates may be sufficient.

Concentration

Injection solution 50 μg/ml = 0.05 mg/ml. Approximately 100 times the potency of morphine (1 ml fentanyl 50 μg ≈ 5 mg morphine)

Pharmacokinetics

Plasma concentration of fentanyl drops rapidly after an intravenous injection. Fentanyl elimination is triphasic with half-lives of approximately 1 minute, 15 minutes, and 6 hours. The central compartment distribution volume is about 15 liters, and the total distribution volume is about 400 liters. Secondary plasma peaks can occur.

Fentanyl is bound to plasma proteins by about 80-85%. It is rapidly metabolized primarily in the liver via CYP3A4, mainly through oxidative N-dealkylation. Clearance is approximately 0.5 l/hour/kg. About 75% of the dose is eliminated within 72 hours. Approximately 10% is excreted unchanged. Half-lives can be prolonged, especially in older individuals or after repeated dosing.

Side effects

Can cause respiratory failure and respiratory depression. May cause muscle stiffness, particularly at high doses, and difficulty in manual ventilation of the patient. It can cause drowsiness and increased fatigue. Can cause bradycardia and hypotension. Muscle rigidity has been observed with increased frequency at high doses and with rapid administration of fentanyl. Bradycardia and possibly asystole may occur if the patient receives an inadequate dose of anticholinergics or if fentanyl is combined with non-vagolytic muscle relaxants. Secondary respiratory depression has been observed.

Warning

Fentanyl reduces the need for hypnotics (inhalation anesthetics) during anesthesia, so the dose of other anesthetics should be reduced. Since adverse hemodynamic effects of fentanyl are more pronounced and frequent in patients with ASA IV than with long-acting opiates, extreme caution should be exercised when administering fentanyl to this patient population.

Clonidine

Sympatholytic. Central alpha₂-agonist. Reduces heart rate, lowers blood pressure, and lessens stress response.

Drug name: Catapresan^®

• Indication: Sedation during mechanical ventilation
• Dosage: Continuous infusion of 15 µg/ml at 2-5 ml/hour, 0.25-1 µg/kg/h. Normal dose 0.33 µg/kg/h. Maximum continuous infusion dose 2 µg/kg/h. Alternatively, 75-150 μg x 4. Same oral dose.
• α1-α2 1:200 agonist, parenteral = enteral dose,
• t_1⁄2 = 8 h – longer with continuous infusion
• Contraindications: Bradycardia, SSS, AV block II-III, combination with Dexmedetomidine, severe hypotension
• Injection solution 150 µg/ml. For continuous infusion 15 µg/ml.

Indication: Hypertension, sympathotonic states, stress conditions. Withdrawal. Stress after head injury or subarachnoid hemorrhage with elevated blood pressure or increased intracranial pressure.

Concentration: Solution 150 µg/ml. For continuous infusion 15 µg/ml.

Side effects: Hypotension, bradycardia, respiratory failure.

Catapresan injection solution 50-150 µg can be administered intravenously, intramuscularly, or subcutaneously up to four times daily. For intravenous infusion, the contents of 1 ampoule (150 µg) should be mixed with approximately 10 ml of sterile saline solution (15 µg/ml) and administered slowly (over about 10 minutes) to avoid transient blood pressure increase. For continuous infusion, dilute to 15 µg/ml.

Warning: Abrupt discontinuation of high doses has been associated with symptoms such as palpitations, anxiety, nervousness, motor restlessness, and in rare cases, blood pressure exceeding untreated levels. Hypersensitivity to clonidine or any excipient, severe bradyarrhythmia caused by sick sinus syndrome or AV block grade II-III, hypotension.

Propofol

Ultra-short-acting intravenous anesthetic. Induction agent for anesthesia or maintenance for sedation in ICU. Propofol has anticonvulsant activity, with very little analgesic properties. Contains 2,6-diisopropylphenol (alkylphenol derivative) in an oil-in-water emulsion [0.1 g fat (1.1 Kcal)/ml] containing 1.0% propofol, 10% soybean oil, 2.25% glycerol, and 1.2% egg phosphatide.

Drug names: Propofol, Diprivan^®, Propolipid^®, Profast^®, Propofol-Lipuro^®

• Dosage: 1-3 mg/kg/hour (2-15 ml/hour, 20 mg/ml). Usual dose: 5-7 ml/hour. Maintenance dose: 0.5-3 mg/kg/h
• Initial dose: 0.5-1 mg/kg/hour, titrated up in increments of 0.5 mg/kg every 5 to 10 minutes
• Onset time: 1-2 minutes
• Duration of bolus dose: 10-15 minutes
• Elimination half-life: 1.8 – 4.1 minutes
• Terminal half-life: ~3 days
• Reduces cerebral blood flow by 50% (lowers ICP) and decreases cerebral metabolic oxygen demand by 18-36%
• Highly lipophilic
• 98% plasma protein-bound
• Injection solution: 10 or 20 mg/ml.

Intravenous anesthetic and sedative agent. Propofol is used for the sedation of ventilated patients over 16 years old in intensive care units. Propofol can also be used with caution in non-ventilated patients for sedation. Propofol (2,6-diisopropylphenol) is a substituted phenol that, when administered intravenously, induces anesthesia. The mechanism of action of propofol is not well understood but is likely mediated through nonspecific membrane binding.

Sedation with propofol for ICU patients

For sedation during intensive care, propofol is recommended to be administered as a continuous infusion. The infusion rate should be adjusted according to the desired depth of sedation. For most patients, sufficient sedation is achieved at a propofol dose of 0.3-4 mg/kg/hour. Propofol should not be administered for sedation in intensive care for patients under 16 years of age. Propofol is widely distributed and rapidly eliminated from the body (total body clearance: 1.5–2 liters/min). Elimination occurs via metabolic processes, mainly in the liver, where it is blood flow-dependent, producing inactive conjugates of propofol and its quinol, which are excreted in the urine. The administration of propofol using a TCI (Target Controlled Infusion) system is not recommended for use in children.

Concentration: 20 mg/ml (ICU), 10 mg/ml (Anesthesia).

Warning: A few reports have been received of adult patients developing metabolic acidosis, rhabdomyolysis, hyperkalemia, and/or rapidly progressive heart failure (in some cases fatal) after being sedated for more than 58 hours at doses exceeding 5 mg/kg/hour.

Midazolam

Intravenous sedative and anxiolytic benzodiazepine.

Drug names: Midazolam^®, Dormicum^®

• Dosage: 1-5 ml/h, 1-25 mg/h. Initial dose: 0.03 mg/kg/hour (1-2 mg iv bolus)
• Maintenance dose: 0.03-0.25 mg/kg/hour titrated to effect. Usual dose: 2-3 ml/h.
• Onset time: 1-3 minutes
• Duration: 30-120 minutes
• Elimination half-life: 1.2-12.3 hours
• Active metabolite: a-hydroxymidazolam
• Antagonist: flumazenil
• 96-98% protein-bound
• Highly lipophilic
• Short-acting agent
• Compatible with IV solutions
• Stable in aqueous solutions
• Causes no pain at the injection site
• Lower incidence of thrombophlebitis
• No adrenal insufficiency
• Injection solution: 1 mg/ml, 5 mg/ml iv

Midazolam is a fast-acting hypnotic benzodiazepine. Midazolam is a potent sedative intravenous drug that requires careful titration and slow administration. Consideration must be given to the patient’s physical status, age, and concomitant medications. The effect occurs approximately 2 minutes after injection. Maximum effect is reached after 5 – 10 minutes. The volume of distribution at steady state is 0.7-1.2 l/kg. Midazolam is 96-98% bound to plasma proteins, primarily albumin. In healthy volunteers, the elimination half-life of midazolam is between 1.5 and 2.5 hours. The half-life and effect are significantly prolonged in severe liver disease.

Dosage: Administered in intravenous infusion 1-2-5 ml/h, 1-10 mg/h. In adults over 60 years old, frail, or chronically ill patients, an initial dose of 0.5 – 1 mg is given. Additional doses of 0.5 – 1 mg may be administered if necessary. Intravenous maintenance dose: doses may vary between 0.03 and 0.2 mg/kg/h. In patients with hypovolemia, vasoconstriction, or hypothermia, the maintenance dose should be reduced. Sedation levels should be regularly evaluated. After prolonged sedation, tolerance may develop, and an increase in dose may be required.

Indications: Sedation during intensive care. For diagnostic or therapeutic examinations. For premedication.

Concentration: Solution: 1 mg/ml, 5 mg/ml. Usually given intravenously but can also be administered orally (1 mg/ml), rectally, or intramuscularly.

Side effects: Respiratory failure, somnolence, increased fatigue.

Warning: Caution in renal insufficiency, old age, muscle weakness, liver failure, and respiratory insufficiency. The effect is potentiated by other centrally acting sedative agents. Prolonged half-life is seen in impaired liver function.

Morphine

Morphine is effective as an analgesic for critically ill patients.

Drug name: Morphine, Morphine

• Can induce histamine release
• Time to onset: 2-3 minutes
• Effect duration: 4-5 hours
• Elimination half-life: 2-3 hours to 4.5 hours
• Initial dose: 0.05 mg/kg (2-10 mg iv) (over 5-15 minutes)
• Maintenance dose: 1-4 mg/h
• Injection solution: 10 mg/ml iv. Can be diluted to 1 mg/ml.

Remifentanil

Intravenous ultra-short-acting opioid for sedation of ICU patients. The recommended concentration for sedation of adults in continuous infusion is 0.05 mg/ml (50 μg/ml).

Drug names: Remifentanil^®, Ultiva^®

• Indication: For analgesia and sedation in the intensive care of mechanically ventilated patients 18 years and older.
• Solution: 50 μg/ml.
• Dosage: 0.05-0.20 μg/kg/min (1-6 ml/hour) at a concentration of 0.05 mg/ml.

Remifentanil is a selective μ-opioid agonist with a rapid onset and very short duration of action. Remifentanil is an esterase-metabolized opioid, metabolized by nonspecific blood and tissue esterases. After the administration of recommended doses of remifentanil, the effective half-life is 3-10 minutes. The average clearance of remifentanil in young healthy adults is 40 ml/min/kg, central distribution volume 100 ml/kg, and distribution volume at steady state 350 ml/kg.

Side effects: Hypotension, apnea, muscle rigidity, particularly in the thorax.

May cause respiratory failure and respiratory depression. May cause muscle rigidity, particularly at high doses, and difficulty in manually ventilating the patient. It may cause somnolence and increased fatigue. Bradycardia and hypotension may occur at high doses. Muscle rigidity has been observed more frequently at high doses and with rapid administration of remifentanil. Bradycardia and possible asystole can occur if the patient is given insufficient doses of anticholinergics or if remifentanil is combined with non-vagolytic muscle relaxants.

Warning: Remifentanil reduces the need for hypnotics necessary to maintain sedation, so the dose of hypnotics should be reduced. Since the adverse hemodynamic effects of remifentanil are more pronounced and frequent in patients with ASA III-IV than with longer-acting opioids, great caution should be exercised when administering remifentanil to this patient group.

Lorazepam

Lorazepam is a suitable agent for long-term treatment of anxiety in critically ill adults. Available as tablet and intravenous solution.

Drug name: Temesta^®, Lorazepam^®

• Initial dose: 0.01-0.1 mg/kg (1-2 mg)
• Maintenance dose: intermittent IV bolus or continuous infusion
• Medium-acting benzodiazepine
• 90-96% protein-bound
• Less lipophilic than diazepam
• Causes less hypotension, lower cost than midazolam
• Onset time: 15-20 minutes
• Duration: 6-8 hours
• Elimination half-life: 12-18 hours

Haloperidol

Haloperidol is a common agent for the treatment of delirium in critically ill adult patients

Drug name: Haldol^® injection solution, tablet

• Initial dose: 2-5 mg IV (Note: caution advised, FASS recommends intramuscular injection)
• Maintenance dose: repeat every 2-4 hours
• Infusion with 10 mg/hour
• Butyrophenone neuroleptic
• Can be given as continuous infusion if 8 boluses of 10 mg have been administered within 24 hours or > 10 mg/hour for 5 consecutive hours
• Onset time: 30-60 minutes
• Duration: 4-8 hours
• Elimination half-life: 33 hours

Sedation of children in ventilators

Objective

• Keep the children calm without stress or pain
• They can be fully awake if tolerated
• Younger children often tolerate being awake with a tube better than adults
• It is important to explain the objective to the parents
• Pain can be difficult to interpret (e.g., abdominal cramps)
• Convince the surgery team to use an epidural anesthesia whenever possible (it simplifies things greatly)

Treatment

• Morphine is the standard treatment for analgesia (normally up to 30 μg/kg/h)
• Rotation to ketobemidone or oxycodone can be done after a week
• Dexmedetomidine is now the first choice for sedation, normally 0.4 -1.4 μg/kg/h (Children < 3 months should probably not exceed 1.0 μg/kg/h)
• Propofol can be used, preferably not for children < 1 year old and preferably not > 4 mg/kg/h, although it facilitates extubation in older children
• Phenobarbital is a good complement that rarely affects breathing or circulation; 5 mg/kg, max 3 times/day can be administered

Suggested strategy for extubation

• Reduce opioid administration to the lowest level you think is necessary, preferably the day before
• Complement with paracetamol
• Lower dexmedetomidine to 0.4-0.8 μg/kg/h, switch to propofol or combine the two
• If midazolam is used, discontinue early in the morning (this is a job for the on-call doctor)
• When ventilator settings allow, turn off propofol, maintain some dexmedetomidine if ongoing, and wait for the patient to wake up
• Larger patients can be extubated with some propofol remaining (1-2 mg/kg/h) to achieve a calmer awakening