Drugs in Intensive Care – Common Agents, Use and Guidelines

Acetylcysteine (acetylcysteine)

Indication: Paracetamol poisoning. Acute liver failure. Poisoning with white or death cap mushroom (amatoxin). Mucolytic in inhalation for COPD.

In paracetamol poisoning, acetylcysteine works by its metabolite cysteine stimulating the liver’s biosynthesis of glutathione. Acetylcysteine is initiated if S-paracetamol exceeds 1000 μmol/l at 4 hours, 700 μmol/l at 6 hours, and 350 μmol/l at 10 hours after overdose. In cases of alcoholism, starvation, dehydration, impaired liver function, or treatment with enzyme-inducing drugs, lower limits should apply: 650, 450, and 230 μmol/l respectively. If treatment with acetylcysteine is started within 8-10 hours after intake, it provides almost 100% protection against liver damage. Then 20 hours of treatment is sufficient. In cases of severe liver impairment, at least 3 PT-INR values with 6-hour intervals must show decreasing levels before ending treatment.

Dosage of N-Acetylcystein in Toxic Hepatic Failure

Concentration: Ampoules with 2000 mg/ampoule diluted according to the specified schedule (200 mg/ml, volume 10 ml).

Side effects: Histamine release, bronchial obstruction, bradycardia, nausea, flushing (redness), itching, urticaria, angioedema, blood pressure drop.

Warning: Inhalation solution is given intravenously! In cases of symptoms of histamine release, one can first try to slow (pause) the infusion during treatment for paracetamol poisoning and treat with an antihistamine (Tavegyl 2 mg IV). Acetylcysteine should be used with caution in people with asthma or those who have previously had bronchospasm.

Alfentanil (Rapifen)

Intravenous sedative and potent analgesic. Alfentanil is a selective μ-opioid agonist with rapid onset and very short effect duration. Intravenous administration gives maximum effect within 90 seconds with a duration of 5-10 minutes. Alfentanil can be used for sedation of intensive care patients in continuous infusion. Alfentanil is chemically related to fentanyl. Pharmacodynamically, alfentanil resembles morphine but has a stronger analgesic and respiratory depressive effect. Used for pain relief and sedation in intensive care of mechanically ventilated patients aged 18 years and older.

Dosage: 0.5-3 mg/hour (1-6 ml/hour), in a concentration of 0.5 mg/ml.

Concentration: Solution 0.5 mg/ml.

Side effects: Can cause respiratory failure and respiratory depression. Can cause muscle rigidity, especially at high doses, and difficulty in manually ventilating the patient. It can cause somnolence and increased fatigue. It can cause bradycardia and hypotension at high doses. Muscle rigidity has been observed with increased frequency at high doses and rapid administration of alfentanil. Bradycardia and possible asystole may occur if the patient has received an insufficient dose of anticholinergics or if alfentanil is combined with non-vagolytic muscle relaxants. Secondary respiratory depression has been observed in rare cases.

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

Alteplase (Actilyse)

Alteplase is a recombinant human tissue plasminogen activator, a glycoprotein that activates plasminogen to plasmin. After intravenous administration, alteplase remains relatively inactive in the systemic circulation. Upon binding to fibrin, activation occurs, leading to the conversion of plasminogen to plasmin, which in turn leads to the dissolution of the fibrin thrombus.

Dosage: In the treatment of acute myocardial infarction with symptom onset < 6 hours, 100 mg is given to individuals over 65 kg. 15 mg is given as a bolus, then 50 mg over 30 minutes, and then 35 mg over 60 minutes. For individuals under 65 kg, 15 mg is given as a bolus, followed by 0.75 mg/kg IV over 30 minutes, and then 0.5 mg/kg over 60 minutes. In the treatment of acute myocardial infarction with symptom onset 6-12 hours, 100 mg is given to individuals over 65 kg. 10 mg is given as a bolus, then 50 mg over 60 minutes, and then 40 mg over 120 minutes. For individuals under 65 kg, 1.5 mg/kg is given. In the treatment of acute pulmonary embolism, 100 mg is given over 2 hours (120 min). For weight under 65 kg, a maximum of 1.5 mg/kg is given. For weight over 65 kg, 100 mg is given. 10 mg (10 ml) is given as a bolus, followed by 90 mg over 2 hours.

Indication: Acute myocardial infarction. Pulmonary embolism. Ischemic stroke.

Concentration: 1 mg/ml. Infusion substance 10 mg, 20 mg, and 50 mg (I+II).

Side effects: Blood pressure drop, bradycardia, respiratory failure.

Warning: Actilyse is contraindicated when there is a high risk of bleeding.

Amiodarone (Cordarone)

Antiarrhythmic. Prolongation of the action potential’s phase 3 in heart fibers by inhibiting the potassium channel. Provides reduced sinus automaticity leading to a decrease in heart rate. Non-competitive alpha and beta-blockade.

Dosage: 5 mg/kg body weight given via intravenous infusion over a period of 20 minutes to 2 hours as slowly as possible depending on the clinical picture. This amount is given as a diluted solution in 250 ml glucose 50 mg/ml. Typically, 300 mg is given over 30 minutes, then 900-1200 mg more over 24 hours, with the infusion rate adjusted based on clinical response. During resuscitation, Cordarone can be given as a bolus dose, 300 mg in 20 ml glucose.

Indication: Severe symptomatic ventricular and supraventricular arrhythmias, including atrial flutter/fibrillation.

Concentration: Injection solution 50 mg/ml. Common strength 50 mg/ml.

Side effects: Bradycardia, blood pressure drop, corneal microdeposits, hypothyroidism.

Warning: Very rare cases of interstitial pneumonitis have been reported with intravenous amiodarone.

ANP (Atrial Natriuretic Peptide)

Atrial natriuretic peptide, atrial natriuretic factor (ANF), or atrial natriuretic peptide (ANP) or HANP (Human Atrial Natriuretic Peptide), is a natriuretic peptide considered a peptide hormone with vasodilatory effect. Its primary function is to contribute to sodium regulation in the kidneys. In the kidneys, it mainly dilates the afferent arteriole, leading to increased glomerular filtration. ANP is a peptide secreted by the atria of the heart. ANP’s main function causes a reduction in expanded extracellular fluid volume (ECF) by increasing renal sodium excretion. ANP is synthesized and secreted by myocardial cells in the atria of the heart. These cells contain volume receptors that respond to increased atrial wall stretch due to increased atrial blood volume.

Concentration: Stock solution (1000 µg in a total of 5 ml) is mixed with 45 ml NaCl 9 mg/ml. The strength of the infusion solution is 20 µg/ml = 20,000 nanograms/ml.

Dosage: Usual dose is 50 nanograms/kg/min

Note: ANP treatment should not be started if the patient is oliguric despite optimal hemodynamics, and if the patient does not respond to adequate doses of furosemide. The patient’s GFR is then very low, and dialysis need is imminent. Successful treatment with ANP is unlikely in these patients.

Argipressin

Argipressin is a synthetic analog of pitressin. Argipressin causes systemic vasoconstriction, thereby increasing peripheral vascular tone with elevated blood pressure. It can also be administered locally and reduces bleeding during laparoscopic surgery for ectopic pregnancy and myomectomy.

Indication: Pronounced hypotension due to vasoplegia (refractory hypotension). Treatment failure with other inotropic drugs in low peripheral vascular resistance.

Dosage: 2.4-4.8 U/hour (which typically equals 6-12 ml/h)

Concentration: 20 U/ml. Dilution of Argipressin is done by diluting 1 ml of 1 ampoule (1 ml = 20 U) with 49 ml Glucose 5% in a 50-ml syringe, giving a concentration of 0.4 U/ml.

Side effects: Headache, flushing, hypotension, pain in the extremities, peripheral edema, blurred vision, nasal congestion, night sweats.

Warning: Caution in – angina pectoris, heart failure, renal failure, poorly controlled hypertension, anaphylaxis, or hypersensitivity to vasopressin.

Clonidine (Catapres)

Sympathetic inhibitor. Central alpha2 agonist. Lowers pulse, blood pressure, and reduces stress response.

Dosage: In continuous infusion 15 µg/ml 2-5 ml/hour, 0.25-1 µg/kg/h. Normal dose 0.33 µg/kg/h. Maximum dose in continuous infusion 2 µg/kg/h.

Indication: Hypertension, sympathetic conditions, 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: Blood pressure drop, bradycardia, respiratory failure.

Catapres injection solution 50-150 µg can be injected intravenously, intramuscularly, or subcutaneously up to four times daily. For intravenous infusion, the contents of 1 ampoule (150 µg) should be mixed with about 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 withdrawal of high doses has been observed to cause symptoms such as palpitations, anxiety, nervousness, motor restlessness, and in rare cases, blood pressure exceeding untreated pressure. Hypersensitivity to clonidine or any excipient, severe bradyarrhythmia caused by sick sinus syndrome or AV block grade II-III, hypotension.

Dantrolene (Dantrium)

Dantrium is a muscle relaxant with postsynaptic action. Dantrolene is an antidote for the onset of malignant hyperthermia. Muscle relaxation counteracts hyperthermia generated by muscle activity. Dantrolene inhibits calcium release from the sarcoplasmic reticulum by antagonizing ryanodine receptors, thereby weakening excitation and contraction in peripheral skeletal muscles. Dantrolene likely has little or no effect on hyperthermia secondary to serotonin syndrome. 

Dosage: Starting dose 2 mg/kg IV (preferably in CVK or large PVK), repeated with 1 mg/kg until symptoms subside. If needed, continue with an infusion of 0.25-0.5 mg/kg per hour. The maximum dose of 10 mg/kg may need to be exceeded in some cases.

Indication: Malignant hyperthermia. Some cases of malignant neuroleptic syndrome with high temperature, rigidity, and marked hypermetabolism.

Concentration: Licensed preparation. Dry ampoules of Dantrium 20 mg are dissolved with 60 ml of sterile water. As many as 35-60 ampoules may be needed for an adult patient! (Call in 5-10 people to prepare the mixture as the preparation is difficult to dissolve). NaCl or glucose solutions should not be used as they are not compatible with dantrolene.

Warning: Drowsiness, impaired or slurred speech, impaired vision. Observe muscle weakness and the associated risk of respiratory failure. Other side effects may include local thrombophlebitis, confusion, and dizziness. Extravasal injection can cause tissue necrosis.

Desmopressin (Octostim)

Hemostatic agent. Octostim is a structural analog of the natural posterior pituitary hormone arginine vasopressin (ADH).

Dosage: 0.3 µg/kg diluted in physiological saline to 10 ml as an intravenous injection over 10 minutes or 0.3 µg/kg as a subcutaneous injection.

Indication: Bleeding. Shortening or normalization of prolonged bleeding time in uremia, liver cirrhosis, congenital or drug-induced platelet dysfunction, and in patients with prolonged bleeding time without detectable etiology. If a positive effect is achieved, the initial dose of Octostim can be repeated 1-2 times at 6-12 hour intervals.

Concentration: Solution 15 µg/ml.

Side effects: Risk of reduced urine production, water retention, and hyponatremia with associated symptoms, headache, nausea, vomiting, weight gain, decreased serum sodium, and in severe cases, seizures.

Warning: Small children and elderly patients, in conditions requiring treatment with diuretics, in disturbed fluid and/or electrolyte balance, and in the risk of increased intracranial pressure.

Contraindications: Unstable angina pectoris, decompensated heart failure, von Willebrand’s disease type 2B.

Dexmedetomidine (Dexdor)

Sympatholytic. Central alpha-2 agonist. Provides sedation, lowers pulse, lowers blood pressure, and reduces stress response. Dexmedetomidine is the S-enantiomer of medetomidine.

Dosage: The infusion rate is adjusted stepwise 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 who are 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 stepwise within the dose range of 0.2 – 1.4 micrograms/kg/hour.

Indication: For sedation of adult ICU patients requiring a sedation level that is not deeper than arousal by verbal stimulation (corresponding to Richmond Agitation-Sedation Scale (RASS) 0 to -3). Sympathotonic conditions with hypertension, stress states, withdrawal.

Concentration: One ml 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: Blood pressure drop, bradycardia, respiratory failure.

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

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

Dihydralazine (Nepresol®)

Vasodilator. Deregistered in Sweden but is available at certain clinics as a licensed medication. Glass ampoules are mixed directly for use 25 mg/2 ml = 12.5 mg/ml.

Concentration: 25 mg/2 ml = 12.5 mg/ml. 12.5 mg/ml. Give 0.5 ml (=6.25 mg) iv in repeated small doses. Provides good blood pressure-lowering effect.

Contraindications for this medication include allergic reactions to this drug or any of its components, ischemic heart disease, coronary artery disease, valvular stenosis, aortic aneurysm, and pericarditis. Patients with a previous medical history of renal failure, liver damage, heart disease, and cerebrovascular disorders must exercise caution when taking this medication. Dihydralazine should not be prescribed to elderly patients or nursing women. Caution must be exercised when prescribing this medication to pregnant women.

Dobutamine (Dobutamine Hameln®)

Positive inotropic drug with weak vasodilatory effect. Dobutamine is a synthetic, sympathomimetic amine. The positive inotropic effect is mainly due to its agonistic effect on the heart’s beta₁ receptors, but also on the heart’s alpha₁ receptors.

Concentration: Normal solution 2 mg/ml.

Receptor activity: α₁ +, β₁++++, β₂ ++, DA-1 0.

Physiological effects: SVR↓, CO↑, HR↑, BP+/-. Binds to and stimulates beta₁ receptors in the heart. Increases contractile force.

Indication: Low cardiac output, heart failure, sepsis.

Dosage: Recommended starting dose is 5 μg/kg/min, then titrated to 2-20 μg/kg/min = 5-40 ml/h for 70 kg.

Dosage activity: < 3 μg/kg/min – usually no effect on blood pressure or blood pressure drop, 5-10 μg/kg/min β₁ effect, increased cardiac output, >10 μg/kg/min – α₁ effect. Increased heart rate.

Side effects: Tachycardia, blood pressure drop in hypovolemia.

Dopamine (Giludop®)

Dopamine is a sympathomimetic catecholamine. The positive inotropic effect is mainly due to its agonistic effect on the heart’s beta₁ receptors, but also on the heart’s alpha₁ receptors. Significant chronotropic effect.

Concentration: Common solution 2 mg/ml

Receptor activity: α₁ ++ , β₁++++, β₂ ++, DA-1 +++

Indication: Refractory hypotension, low cardiac output, heart failure, oliguria, sepsis.

Dosage: 3-15 μg/kg/min = 7-40 ml/h for 70 kg.

Dosage activity: < 3 μg/kg/min – DA effect, 5-10 μg/kg/min β₁ effect, increased heart rate, > 10 μg/kg/min – α₁ effect.

Side effects: Tachycardia, arrhythmias, renal intestinal hypoperfusion, psychiatric symptoms, pituitary dysfunction.

Ephedrine

Ephedrine is a naturally occurring alkaloid. Ephedrine raises blood pressure by stimulating adrenergic alpha and beta receptors. Ephedrine acts partly directly on the receptors but mainly by releasing endogenous noradrenaline, which in turn affects the receptors. The positive inotropic effect is mainly due to its agonistic effect on the heart’s beta₁ receptors, but also to some extent on the heart’s alpha₁ receptors.

Receptor activity: α₁ +, β₁ +++, β₂ ++, DA-₁ 0.

Physiological effects: Provides slightly increased inotropy, chronotropy, and blood pressure elevation. Releases noradrenaline. Increased cardiac output (CO), increased blood pressure, and mean arterial pressure. Increased SVR, decreased CO, increased HR, increased BP. Short-term effect for 5-15 minutes with intravenous administration. Somewhat more prolonged effect with subcutaneous or intramuscular administration.

Indication: Temporary blood pressure drop, vasodilation, bradycardia, blood pressure drop after spinal anesthesia and epidural anesthesia, blood pressure drop after anesthesia induction, bronchial asthma.

Side effects: Tachycardia, extrasystoles, arrhythmias, atrial fibrillation, myocardial ischemia.

Concentration: Solution 50 mg/ml. Common strength is 5 mg/ml (diluted) or 50 mg/ml.

Dosage: 5-10 mg IV. Common starting dose 5 mg IV, adjusted according to blood pressure and pulse. 25-50 mg can be given IM. Intramuscular dose can be given simultaneously with intravenous dose, e.g., 5 mg IV plus 25 mg intramuscularly in connection with spinal anesthesia.

Dosage activity: 5 – 10 mg usually provides moderate effect on blood pressure, with unchanged CO, > 10 mg also increases CO.

Eptacog alfa (NovoSeven)

NovoSeven is a hemostatic agent. It contains recombinant coagulation factor VII.

Dosage: An initial dose of 90 µg/kg body weight is recommended. The dose should be repeated after 2 hours and then every 2-3 hours during the first 24-48 hours depending on the procedure and the patient’s general condition.

Indication: Major bleeding. NovoSeven is indicated for the treatment of major bleeding and for the prevention of bleeding during surgical or invasive procedures in certain risk groups. These risk groups include congenital or acquired hemophilia, isolated factor VII deficiency, Glanzmann’s thrombasthenia.

Concentration: Solution 1 mg/ml. Prepare the solution and administer it as an intravenous injection over 2–5 minutes.

Side effects: Arterial thromboembolic events (cerebral artery occlusion, cerebrovascular event), venous thromboembolic events (pulmonary embolism, hepatic artery embolism, and deep vein thrombosis), angina pectoris, nausea, fever, erythematous rash. Lack of effect.

Warning: In conditions where tissue factor is expected to be present in higher amounts than normal, there may be a risk of thrombotic disease or induction of disseminated intravascular coagulation (DIC).

Contraindications: Hypersensitivity to the active substance or to mouse, hamster, or bovine protein.

Fentanyl

Fentanyl is a potent opioid and a short-acting intravenous anesthetic and analgesic. Fentanyl 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 of action. Despite the rapid onset, the maximum analgesic and respiratory depressant effect is achieved only after a few minutes. Typically, the analgesic effect of an intravenous injection of 100 micrograms of fentanyl lasts about 30 minutes. In pharmacodynamic terms, fentanyl is similar to morphine but has more potent analgesic and respiratory depressant effects. Even in large bolus doses, fentanyl has often been used for anesthesia induction in patients with heart disease due to its cardiovascular stability and its ability to suppress hemodynamic responses to intubation.

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

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

Dosage

In anesthesia procedures, the usual initial dose of fentanyl for adults is 50-100-200 μg, 1-2-4 ml, slowly injected intravenously. The dose can be repeated 20-30-45 minutes after the initial dose. Secondary respiratory depression has been observed in cases where large doses have accumulated. There is a risk of accumulation with continuous infusion.

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

• Intubation dose for general anesthesia: 1–8 μg/kg IV (70 kg = 70-600 μg = 2-12 ml).
• For children 2 – 12 years, 1-3 μg/kg is given in combination with inhalational anesthesia.

Fentanyl can be given as an infusion.

• Maintenance dose for surgical anesthesia: 0.1-0.70 μg/kg/min.
• Standard dose: 0.15 μg/kg/min.
• Intubation dose: 1-2 μg/kg.

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

Concentration

Solution 50 μg/ml.

Strength

Approximately 100 times the strength of morphine. (1 ml fentanyl ~ 10 mg morphine).

Side Effects

May cause respiratory failure and respiratory depression. May cause muscle rigidity, especially at high doses, and difficulties in manually ventilating the patient. It may cause drowsiness and increased fatigue. May 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 (inhalational anesthetics) required to maintain anesthesia, so the dose of other anesthetics should be reduced. As the adverse hemodynamic effects of fentanyl are more pronounced and frequent in ASA IV patients than with long-acting opiates, great caution should be exercised when administering fentanyl to this patient population.

Fentanyl Transdermal (Patch)

After the first application of the patch, the serum concentration of fentanyl gradually increases. Maximum effect occurs after about 8 hours. It usually levels off after 12–24 hours and remains relatively constant during the rest of the 72-hour application period. Steady-state serum concentration is achieved at the end of the second 72-hour application and is maintained during subsequent applications of a depot patch of the same size. Due to accumulation values for AUC and Cmax during a dosage interval at steady state are approximately 40% higher than after a single application. High variability in plasma concentrations between individuals has been observed.

Side Effects

May cause respiratory failure and respiratory depression.

Epoprostenol (Flolan)

Prostacyclin, a metabolite of arachidonic acid. The main pharmacological effects of prostacyclin (PGI₂) consist of a marked vasodilation of the pulmonary vascular bed and systemic circulation, inhibition of platelet aggregation, and antiproliferative effects. The half-life in plasma is 2-3 minutes. The vasodilatory effect ceases within 30 minutes after stopping the infusion.

Dosage: 500 μg in a dry ampoule is dissolved with 10 ml of the supplied diluent. Add the dissolved Flolan to the remaining diluent, a total of 50 ml. The strength is now 10 µg/ml. 4 ml of Flolan at a strength of 10 µg/ml is added via the supplied particle filter into a 50 ml syringe with 36 ml NaCl 9 mg/ml. The strength is 1 µg/ml. Start dose is 0.24 µg/kg/hour = 0.24 ml/kg/hour. The effect comes at 0.6 – 1 µg/kg/hour = 0.6 – 1 ml/kg/hour.

Indication: Pulmonary hypertension, right heart failure.

Concentration: 1 µg/ml. Given as an intravenous infusion into a central line.

Side effects: Blood pressure drop, prolonged bleeding time, jaw pain, headache, leg pain, and diarrhea. All are dose-dependent.

Warning: Side effects include chest rigidity, breathing difficulties, irregular heartbeat, skin hemorrhages, hematuria.

Fibrinogen (Riastap)

Human fibrinogen concentrate.

Dosage: To calculate the individual dose, the functional fibrinogen level should be determined. If the patient’s fibrinogen level is unknown, an intravenous dose of 70 mg per kg body weight is recommended. The target level (>2 g/l) for major bleeding (e.g., head injuries or brain hemorrhages) should be maintained for seven days. The dose of fibrinogen (mg/kg body weight) to be administered = [target level (g/l) – measured level (g/l)] / 0.017 (g/l per mg/kg body weight). Usually, 1-2-4 g is administered intravenously per occasion, repeated if necessary after checking bleeding parameters. One gram of fibrinogen raises plasma levels by approximately 0.5 g/l.

Indication: Major bleeding, traumatic bleeding. Treatment of bleeding in patients with congenital hypo- or afibrinogenemia with bleeding tendency. The normal fibrinogen level in plasma is 1.5-4.5 g/l. The critical fibrinogen level in plasma, below which bleeding may occur, is 0.5-1.0 g/l. In cases requiring major surgery, it is essential to accurately monitor replacement therapy through coagulation tests.

Concentration: Powder for solution 1 g.

Side effects: Thromboembolic events including myocardial infarction and pulmonary embolism. Lack of effect.

Warning: Increased thromboembolism risk exists in patients with congenital deficiency when treated with human fibrinogen concentrate, especially at high or repeated dosing. Patients receiving human fibrinogen concentrate should be closely monitored for signs and symptoms of thrombosis.

Contraindications: Hypersensitivity to the active ingredient or any excipient.

Glypressin (Terlipressin)

Vasoconstrictor. Terlipressin initially has a self-effect but is converted to lysine-vasopressin by enzymatic cleavage. Doses of 1 and 2 mg are effective in reducing portal pressure and lead to significant vasoconstriction. The desired concentration of lysine-vasopressin in plasma is initially achieved after approximately 30 minutes and reaches a peak value after 60 to 120 minutes. Adjuvant to failing norepinephrine treatment in sepsis with vasoplegia.

Dosage: Initially, an intravenous injection of 2 mg Glypressin injection solution is given every four hours. The treatment should continue until the bleeding has been controlled for 24 hours, but a maximum of 48 hours. After the initial dose, the dose may be adjusted to 1 mg intravenously every four hours for patients weighing < 50 kg or if the patient experiences side effects.

Indication: Bleeding esophageal varices. Sepsis with vasoplegia.

Concentration: Solution 1 mg/ml.

Side effects: Pallor, increased blood pressure, abdominal pain, nausea, diarrhea, and headache.

Contraindications: Pregnancy.

Warning: Blood pressure, heart rate, and fluid balance should be monitored during treatment. The injection must be given intravenously to prevent local necrosis at the injection site.

Heparin (Heparin)

Heparin, which normally occurs in the body bound to protein, is a strongly acidic, sulfated glycosaminoglycan (mucopolysaccharide) with anticoagulant effect. In combination with the co-factor, antithrombin III, heparin affects several steps in the coagulation mechanism, providing a blood-thinning effect. Heparin is used in the treatment of thromboembolic events such as pulmonary embolism or deep vein thrombosis.

Dosage

• In the treatment of deep vein thrombosis, a bolus dose of 5000 E (1 ml) i.v. is given for weight under 85 kg.
• For weight over 85 kg, a bolus of 7500 E (1.5 ml) i.v. is given.
• For the treatment of pulmonary embolism, a bolus of 7500 E (1.5 ml) i.v. is given.
• For massive DVT/PE: larger bolus (100-150 E/kg).
• In case of increased bleeding risk, a bolus of 2500 E i.v. is given, except for massive pulmonary embolism/DVT. In suspected pulmonary embolism, bolus and infusion are given while awaiting diagnosis. Thereafter, a continuous infusion of heparin, heparin drip, is given. 15000 E (3 ml) is added to 500 ml 0.9% NaCl or 7500 E (1.5 ml) in 250 ml 0.9% NaCl. The drip is started simultaneously with the bolus dose.
• For weight > 60 kg and age < 65 years, give 42 ml/h. For other adults, give 36 ml/h. The treatment effect is monitored with APTT controls. The first APTT control is after 6 hours. APTT should be 1.5-3 times the reference value, i.e., 60-120 seconds (increased bleeding risk 50-80 seconds).

Indication

Anticoagulation. Deep vein thrombosis (DVT), pulmonary embolism. Intravascular coagulation, peritendinitis crepitans. Extracorporeal circulation in connection with cardiovascular surgery and hemodialysis.

Side effects

Bleeding, thrombocytopenia, transient liver effects.

Concentration

5000 IE/ml, 25000 IE/ml.

Warning

Heparin is contraindicated when there is a high risk of bleeding. Caution is recommended with thrombocytopenia and platelet function defects (even drug-induced), as well as in severe liver and renal insufficiency.

Human Immunoglobulin (Gammagard – IVIg)

Gammagard S/D contains primarily immunoglobulin G (IgG) with a broad spectrum of antibodies against infectious agents. Gammagard S/D has immediate and complete bioavailability in the recipient’s circulation after intravenous administration. It is distributed relatively quickly between plasma and extravascular fluid, reaching intra- and extravascular equilibrium after approximately 3-5 days.

Dosage: For treatment of an acute episode, 0.8–1.0 g/kg body weight is given on the first day, which may be repeated once within 3 days, or 0.4 g/kg body weight daily for 2 to 5 days. Dosage varies with the indication.

Indication: Guillain-Barré syndrome (GBS), primary immunodeficiency syndromes, e.g., congenital agammaglobulinemia and hypogammaglobulinemia, common variable immunodeficiency, severe combined immunodeficiency, Wiskott-Aldrich syndrome, myeloma or chronic lymphocytic leukemia (CLL) with severe secondary hypogammaglobulinemia and recurrent infections. Idiopathic thrombocytopenic purpura (ITP) in children or adults with high bleeding risk or before surgery to correct platelet count. Kawasaki disease.

Concentration: Powder for 2.5-5-10 g injection vial.

Side effects: True hypersensitivity reactions are rare. They may occur in very rare cases of IgA deficiency with anti-IgA antibodies. In rare cases, human normal immunoglobulin can induce a blood pressure drop with an anaphylactic reaction, even in patients who have previously tolerated treatment with human normal immunoglobulin.

Warning: In patients at risk of acute renal failure or thromboembolic side effects, IVIg products should be administered at the lowest possible infusion rate and dose. In all patients, administration of IVIg requires adequate fluid intake before the IVIg infusion starts, monitoring of urine output, monitoring of serum creatinine levels, and avoiding the use of loop diuretics concurrently. Hypersensitivity to homologous immunoglobulins, especially in the very rare cases of IgA deficiency when the patient has antibodies against IgA.

Hydrochloric Acid (HCl)

Dosage: H⁺ ion deficit (mEq) = 0.3 x weight (kg) x (measured HCO₃ – desired HCO₃ [mEq/L]). The rate of a hydrochloric acid infusion should be 0.1 – 0.2 mEq/kg/hour. For example, 0.1 N solution IV at 100 ml/h provides about 10 mEq/h.

Indication: Severe metabolic alkalosis.

Concentration: Stock solution HCl 5 mmol/ml, 10 ml of the stock solution (= 50 mmol) diluted in 240 ml Glucose 5% or Sodium chloride 9 mg/ml = 0.2 mmol/ml.

Side effects: Vascular irritation. Metabolic acidosis.

Warning: Must only be administered slowly in a central venous catheter. Can cause vascular damage and tissue necrosis. Should be administered from a glass bottle. HCl must not be mixed with other solutions and should be infused as the sole medication through a separate channel in a central venous catheter.

Iloprost (Ventavis)

A synthetic prostacyclin analog that is inhaled via a nebulizer. Provides selective reduction of vascular resistance in the pulmonary circulation.

Indication: Primary pulmonary hypertension (PPH).

Dosage: 2.5-5 micrograms per dose x 6-9/day. When starting treatment with iloprost, the first inhaled dose should be 2.5 micrograms iloprost given through the nebulizer’s mouthpiece. If the dose is well tolerated, it should be increased to 5 micrograms iloprost and maintained at that level. If the 5-microgram dose is poorly tolerated, the dose should be reduced to 2.5 micrograms.

Concentration: Solution for nebulizer 20 micrograms/ml.

Side effects: Bleeding, thrombocytopenia, headache, vasodilation, flushing, chest pain, cough, peripheral edema.

Warning: The vasodilatory effect in the lungs after inhalation of iloprost has a short duration (one to two hours). Blood pressure should be monitored before starting treatment with Ventavis. In patients with low systemic blood pressure and in patients with postural hypotension or who are taking medications that lower blood pressure, caution should be exercised to avoid further hypotension. Ventavis treatment should not be initiated in patients with systolic blood pressure below 85 mmHg.

Isoprenaline

Isoprenaline is a sympathomimetic amine. The positive inotropic effect is mainly due to the agonistic effect on the heart’s beta1 receptors and beta2 receptors, but also on the heart’s alpha1 receptors. Isoprenaline is a vasodilator with a pronounced positive chronotropic effect.

Concentration: Common strength 0.01 mg/ml after dilution

Receptor activity: α1 none, β1++++, β2 ++++, DA-1 none. Positive chronotropic and inotropic effects on the heart. Potent vasodilation and increased heart rate. Increased cardiac output (CO), decreased diastolic blood pressure, and mean arterial pressure.

Physiological effects: decreased SVR, CO↑↑, HR↑↑, decreased BP, bronchodilation.

Indication: Circulatory shock, bradycardia, AV block III, refractory hypotension, cardiac arrest, severe heart failure with low CO, cardiogenic shock, certain severe poisonings.

Dosage: 10-20 ng/kg/min. Common starting dose 10 ng/kg/min, adjusted according to blood pressure. Maximal dose 150 ng/kg/min.

Dose activity: < 0.05 μg/kg/min – usually moderate effect on blood pressure, possible blood pressure drop, increased CO, 0.05-0.1 μg/kg/min β1 effect, increased cardiac output, increased heart rate.

Side effects: Tachycardia, blood pressure drop, arrhythmias.

Ketamine (Ketalar)

Anesthetic for intravenous or intramuscular administration for anesthesia induction and maintenance. Provides analgesia and dissociative anesthesia. Can also be given orally for sedation. Induction and maintenance of anesthesia during diagnostic and surgical procedures, either as the sole anesthetic or in combination with other anesthetics. Ketamine can be given before the establishment of or as a complement to regional anesthesia, even in emergency fracture surgery. Ketamine or ketanest can be given in continuous infusion for the treatment of severe pain alone or in addition to other pain treatments. Ketamine has been described to provide a rapidly acting antidepressant effect and is now being tested in depression and severe pain conditions. (For this purpose, ketamine can be given in a nasal spray).

• Ketalar = Ketamine in racemic form (50% Ketamine-R + 50% Ketamine-S)
• Ketanest = Ketamine-S = Esketamine. Ketanest is about twice as potent as Ketalar and causes less cognitive impact.

Ketamine is an NMDA receptor blocker and provides a so-called dissociative anesthesia with effective pain relief through selective interruption of association pathways in the brain. The patient falls asleep easily after induction and is put into a hypnotic state where pain or perception (other sensory impressions) is no longer experienced normally. The state is dreamlike, and vivid dreams of a hallucinatory nature are often described. The dreams can be both pleasant and unpleasant. The patient has increased sensitivity to sound, so the environment should be calm, quiet, and peaceful. The depth of anesthesia can be difficult to assess as the patient no longer reacts to sound, light, touch, or address without appearing to be asleep. In sub-anesthetic doses, ketamine has an analgesic effect, probably due to interaction with biogenic amine and endogenous opioid systems. Ketamine usually does not affect reflexes in the pharynx and larynx, and muscle tone remains normal or slightly increased. Cardiovascular and respiratory-stimulating effects allow ketamine to be given to high-risk patients in hypovolemic shock. The analgesic effect can be used as a complement to regional anesthesia or in mass casualty situations/disaster contexts.

Concentration

10 mg/ml for intravenous use, 50 mg/ml for intramuscular use.

Induction anesthesia

1-2 mg/kg iv, alternatively (5)-10 mg/kg im (+ midazolam 1-3 mg). An intravenous dose of 2.0 mg/kg body weight provides surgical anesthesia within one minute after injection, and the anesthetic effect lasts for 5-15 minutes. Intramuscular dosing 10.0 mg/kg body weight provides surgical anesthesia within 3-5 minutes after injection with a duration of 12-25 minutes. To achieve prolonged anesthesia or analgesia, ketamine can be given in infusion (0.5-4 mg/kg/h) or syringe pump for even administration, e.g., during anesthesia of a patient in hemorrhagic shock. The initiation of anesthesia is followed by temporary tachycardia, elevation of blood pressure, and cardiac output, which return to baseline values within 15 minutes after injection. (Preferably quiet in the room or headphones on the patient). Orally, ketamine provides good sedation after 10-15 minutes and lasts for about 30-45 minutes. It can be given diluted in juice in a dose of about 4-5 mg/kg.

Maintenance dose anesthesia

• 0.5-4 mg/kg/h iv in decreasing dosage
• Postoperative pain relief: 5-15 mg bolus
• Maintenance infusion for postoperative pain relief: 0.05-0.5 mg/kg/h

Cave:

Hypertension (relative contraindication). In case of liver failure, the dose should be reduced. Risk of abuse

exists with non-medical use.

Ketamine in pain treatment

Ketamine/Ketanest (Esketamine) in low doses for pain

Ketamine (S and R, see below), which is an NMDA receptor blocker, modulates both surgically induced and drug-induced hyperalgesia at doses significantly lower than those required for general anesthesia. (Hyperalgesia = increased response to a painful stimulus.) Ketamine has an opioid-sparing effect.

There are two isomers: Ketamine-S and Ketamine-R

• Ketanest = Ketamine-S = Esketamine. Ketanest is about twice as potent as Ketalar and causes less cognitive impact.
• Ketalar = Ketamine in racemic form (50% Ketamine-R + 50% Ketamine-S).

Indications

• Expected postoperative pain problems
• Amputation (upper, lower extremity)
• Acute phantom pain
• Patients with chronic pain + acute pain
• Ongoing high opioid medication (opioid-tolerant patient) + acute pain
• Substance abuse history (when you want to avoid opioids) + acute pain

Dosage

Perioperative Ketanest infusion; low-dose infusion (as an adjunct to local, regional, or general anesthesia)

• Operation start: 0.1 – 0.3 mg/kg bolus iv
• Maintenance dose: 0.1 – 0.3 mg/kg/h iv
• After the last suture is placed: 0.03 mg/kg/h iv
• Postoperatively for 12 – 72 hours: 0.03 – 0.06 mg/kg/h intravenously.

Postoperative Ketanest or Ketanest for non-operated patients

• Single bolus doses: 0.1 mg/kg iv
• And/or low-dose infusion:
• Loading dose (bolus dose): 0.1 mg/kg iv
• Maintenance dose: 0.03 – 0.06 mg/kg/h iv, given for 12 – 72 hours.

Drug combinations and recommendations

• Ketanest is preferably combined with low-dose midazolam or another benzodiazepine.
• Increased salivation is common with Ketanest treatment; therefore, give Glycopyrronium (Robinul) or Atropine iv.
• Significant interactions are absent when Ketanest is given in low doses, which means that other prescribed analgesics (paracetamol, NSAIDs, Cox-2 inhibitors, opioids, clonidine, gabapentin, pregabalin, local anesthetics) should be given.
• Ketanest should not be mixed with morphine in the same iv-PCA pump.
• Ketanest is not recommended as iv-PCA.
• The seizure threshold may be lowered in combination with xanthine derivatives (e.g., Aminophylline and Theophylline), and therefore these combinations should be avoided.
• The drug should not be used together with Ergometrine (Ergotamine).

Monitoring and documentation

• Patients receiving iv low-dose Ketanest infusion are usually monitored in Postop/ICU.
• Document sedation level, NRS/VAS, respiratory rate, SaO2, pulse, and blood pressure.
• Actively inquire about nightmares, hallucinations, and visual disturbances during control.

Side effects

• Nightmares, hallucinations, or visual disturbances seem to be insignificant with low-dose infusion and/or single bolus. Give 1 – 3 mg Midazolam iv (or another benzodiazepine) as needed.
• Increased salivation. Give Robinul (Glycopyrronium) or Atropine iv.

Contraindications

• Hypersensitivity to the active ingredient or any excipient.
• Eclampsia and pre-eclampsia.
• Patients for whom an increase in intracranial pressure poses a serious risk.
• Patients for whom an increase in blood pressure poses a serious risk.

Labetalol (Trandate®)

Antihypertensive medication. Labetalol lowers blood pressure by blocking peripheral arteriolar alpha-adrenoceptors, thereby reducing peripheral resistance. Simultaneously, with beta-blockade, it protects the heart from reflex sympathetic activity that would otherwise occur. Labetalol blocks beta1-, beta2-, and alpha1-receptors. Heart rate is lowered less with labetalol treatment compared to most β-receptor blockers. Effects are usually seen within 5 minutes. It can be administered as an intravenous bolus injection or intravenous infusion using a volumetric pump. It can be given through both central venous catheters (CVC) and peripheral venous catheters (PVC).

Indications:
Hypertension, sympathicotonic states, stress conditions. Hypertension following head trauma or subarachnoid hemorrhage with elevated blood pressure or increased intracranial pressure.

Concentration:
Undiluted solution 5 mg/ml. For continuous infusion, dilute to 1 mg/ml.

Dosage
Bolus injection:
Inject the undiluted solution (5 mg/ml). Administer 5–10 mg per dose. The dose is determined by the degree of hypertension and the indication for acute blood pressure reduction. Administer slowly over approximately 30 seconds (10 mg/min). The treatment can be repeated every 5 minutes until the desired effect is achieved. The total dose by injection should not exceed 200 mg (40 ml). Maximum effect is usually reached within 5 minutes and lasts about 6 hours, but may extend up to 18 hours.

Continuous infusion:
For initiation and low infusion rates: Mix 40 ml of Labetalol 5 mg/ml (200 mg) with 160 ml of 5% Glucose or 0.9% NaCl to a concentration of 1 mg/ml (total volume 200 ml).
For high infusion rates: Mix 200 ml of Labetalol 5 mg/ml (1000 mg) with 800 ml of 5% Glucose or 0.9% NaCl to a concentration of 1 mg/ml (total volume 1000 ml).

Starting dose: 50 mg/h (for pronounced hypertension, consider starting with a bolus injection). Titrate upward by 10 mg/h every 10 minutes until the desired effect is achieved. The effective dose is usually 50–200 mg/h (50–200 ml/h). The infusion is stable for 24 hours after preparation. Tapering of treatment should be done in consultation with the attending physician.

Side effects:
Hypotension, bradycardia, respiratory failure.

Warning:
Hypersensitivity reactions such as flushing, itching, skin rashes, and dyspnea. Elevated liver enzymes. Nasal congestion.

Levosimendan (Simdax®)

Calcium sensitizer with a positive inotropic effect.

Physiological effects: Increased cardiac contractility, CO↑, HR↑, vasodilation, increased ejection fraction, blood pressure reduction, decreased SVR. Levosimendan increases contractility and decreases both preload and afterload without negatively affecting diastolic function. Levosimendan activates so-called “stunned” myocardium.

Dosage: 6-12 μg/kg/min for 10 minutes followed by a continuous infusion of 0.1 μg/kg/min for 24 hours. Common starting dose 6 μg/kg/min, adjusted according to blood pressure. Avoid bolus dose if there is a risk of blood pressure drop.

Indication: Short-term treatment of acute decompensated severe chronic heart failure (ADHF) when conventional treatment is insufficient and inotropic support is deemed appropriate.

Concentration: Solution 2.5 mg/ml, usual strength 0.025 mg/ml or 0.05 mg/ml.

Side effects: Tachycardia, blood pressure drop, headache, atrial fibrillation, ventricular arrhythmias, hypokalemia.

Dose-activity: 0.05-2 μg/kg/min – usually moderate effect on blood pressure, blood pressure drop.

Contraindications: Severe hypotension and tachycardia, mechanical obstruction in the left ventricle, Torsade de Pointes, severely impaired renal function. Correct hypokalemia, hypovolemia.

Medication name: Simdax®

Lorazepam

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

• 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
• Medication name: Temesta®, Lorazepam®

Milrinone (Corotrop®)

Milrinone is a bipyridine derivative with both positive inotropic and vasodilatory effects but with minimal chronotropic effect.

Receptor activity: Phosphodiesterase III inhibitor.

Physiological effects: SVR↓, CO↑, HR↑, BP+/-. Increases cardiac contractile force and stroke volume, vasodilator.

Indication: Severe heart failure, cardiogenic shock.

Concentration: Solution 1 mg/ml. Common strength for continuous infusion is 0.1 mg/ml (100 µg/ml) or 0.15 mg/ml (150 µg/ml).

Dosage: Initially, a slow (10 minutes) intravenous injection of 50 µg/kg. Then a continuous infusion of 0.37-0.75 μg/kg/min. Common starting dose 0.5 μg/kg/min, adjusted according to blood pressure. In the majority of patients, hemodynamic improvement is noted within 5-15 minutes. Doses in the range of 0.375-0.50 µg/kg/min tend to maximize the initial improvement in cardiac output, while doses in the range of 0.50-0.75 µg/kg/min tend to maximize improvements in preload and afterload parameters such as PCW pressure (pulmonary capillary wedge), mean arterial pressure, and systemic vascular resistance (SVR).

Dose activity: <0.375 μg/kg/min – usually moderate effect on circulation, 0.5-0.75 μg/kg/min β1 effect, blood pressure increase, increased CO and EF.

Contraindications: Hypovolemia, obstructive aortic or pulmonary valve disease. Exercise caution during acute myocardial infarction.

Side effects: Hypotension, increased cardiac oxygen consumption, tachycardia, VES, VT.

Magnesium (Magnesium)

Essential mineral. Antiarrhythmic. Magnesium acts as the body’s own calcium antagonist and a sympatholytic. It is a moderate vasodilator. Reduces sinus automaticity in the heart, leading to a decrease in heart rate during intravenous administration. Causes moderate blood pressure reduction and heart rate reduction and counteracts stress-induced ectopic beats. Relaxes smooth muscle. Raises the seizure threshold and has an anticonvulsant effect.

Dosage: 20 mmol is given via intravenous infusion over a period of 20-30 minutes. Thereafter, an infusion of an additional 20 mmol of magnesium is given over 20 hours. Rule of thumb: 20 mmol in 20 minutes + 20 mmol in 20 hours. Higher doses can be given in the treatment of eclampsia.

Indication: Severe symptomatic ventricular and supraventricular arrhythmias, including atrial flutter/fibrillation, especially in sympathetic conditions with heart failure. Eclampsia with seizures. Hypertension. Severe asthma.

Concentration: Common strength in ready solution is 0.2 mmol/ml. 20 ml solution 1 mmol/ml (20 mmol) diluted in 100 ml NaCl. Concentration in undiluted solution is 1 mmol/ml in a 10 ml plastic ampoule.

Side effects: Blood pressure drop, bradycardia, respiratory failure. Causes flushing and a feeling of warmth. Can cause pain at the injection site. Flatulence.

Warning: Exercise caution in renal insufficiency and respiratory insufficiency.

Methylnaltrexone (Relistor)

Opioid antagonist for parenteral use (subcutaneous injections) against opioid-induced constipation. Methylnaltrexone is a quaternary amine that cannot penetrate the blood-brain barrier and thus acts selectively on intestinal receptors, providing no systemic effect but only a local effect in the intestines. Relistor is primarily indicated for cancer patients but can also be used for intensive care patients with opioid-induced constipation. Few studies are available on intensive care patients, but it likely has the same clinical effect as oral naloxone. Opioids inhibit intestinal peristalsis by releasing acetylcholine in the parasympathetic nervous system, resulting in increased tone, decreased fluid secretion, and reduced intestinal peristalsis. Methylnaltrexone increases bowel transit and reduces oro-rectal transit time. It can be used simultaneously with other treatments for constipation, such as Movicol and laxoberaldrops.

Dosage: 8-12 mg x 1 sc.

Indication: Opioid-induced constipation.

Concentration: Injection solution 12 mg/0.6 ml.

Metolazone (Zaroxolyn®)

Metolazone is a thiazide-like diuretic marketed under the brand names Zytanix, Metoz, Zaroxolyn, and Mykrox. It is mainly used to treat heart failure and high blood pressure. Metolazone indirectly reduces the amount of water absorbed into the bloodstream by the kidney, thereby decreasing blood volume and increasing urine volume. It potentiates other diuretics such as furosemide in moderate renal failure. Can be used as adjunctive therapy in renal failure and reduced effect of furosemide. Can be given in edema when furosemide is not sufficiently effective.

Strength: 5 mg/tablet. Available only in tablet form.

Dosage: 5-10 mg/day. Preferably given only once per day.

Warning: Hyponatremia may occur.

Metoprolol (Seloken®)

Selective beta-blocker.

Physiological effects: HR↓, BP↓, CO↓, decreased ejection fraction (EF), decreased contractility, blood pressure reduction, unchanged SVR.

Dosage: In continuous IV infusion 1-4 mg/h, adjusted according to pulse and blood pressure, 1-4 ml/h. Can be given in bolus doses of 1-2 mg at a rate of 1-2 mg/min.

Indication: Tachycardia, hypertension, supraventricular and ventricular tachyarrhythmias, angina, myocardial ischemia.

Concentration: Solution 1.0 mg/ml.

Concentration for infusion: Common strength 1 mg/ml (or 0.05 mg/ml).

Side effects: Bradycardia, blood pressure drop,

asystole, bronchospasm, sleep disturbances.

Contraindications: Bronchospasm, severe hypotension, severe heart failure, Takotsubo cardiomyopathy, hypovolemia, mechanical obstruction in the left ventricle, hyperkalemia, hypoglycemia. Caution when used concurrently with other antiarrhythmics, digitalis, or amiodarone.

Midazolam (Midazolam®)

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 other medications. The effect begins approximately 2 minutes after the injection. The maximum effect is reached after 5 – 10 minutes. The distribution volume at steady state is 0.7-1.2 l/kg. Midazolam is 96 – 98% bound to plasma proteins, mainly 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: Given in intravenous infusion 1-2-5 ml/h, 1-10 mg/h. In adults over 60 years of age, frail or chronically ill patients, an initial dose of 0.5 – 1 mg is given. Additional doses of 0.5 – 1 mg can be given if necessary. Intravenous maintenance dose: doses may vary between 0.03 and 0.2 mg/kg/hour. In patients with hypovolemia, vasoconstriction, or hypothermia, the maintenance dose should be reduced. The level of sedation should be regularly evaluated. After prolonged sedation, tolerance may develop, and an increase in dose may be necessary.

Indication: Sedation in connection with intensive care or for diagnostic or therapeutic procedures. For premedication.

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

Side effects: Respiratory failure, somnolence, increased tiredness.

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

Milrinone (Corotrop®)

Milrinone is an inotropic drug that acts as a phosphodiesterase III inhibitor.

Physiological effects: SVR↓, CO↑, HR↑, BP+/-. Increases contractility and stroke volume. Vasodilator.

Dosage: Initially a slow (10 minutes) intravenous injection of 50 µg/kg. Then a continuous infusion of 0.37 μg/kg/min to 0.75 μg/kg/min. The usual starting dose is 0.5 μg/kg/min, adjusted based on blood pressure. In the majority of patients, hemodynamic improvement is noted within 5-15 minutes. Doses in the range of 0.375-0.50 µg/kg/min tend to maximize the initial improvement in cardiac output, while doses in the range of 0.50-0.75 µg/kg/min tend to maximize improvement in preload and afterload parameters such as PCW pressure, mean arterial pressure, and systemic vascular resistance.

Dosage activity: <0.375 μg/kg/min – usually moderate effect on circulation, 0.5-0.75 μg/kg/min β₁-effect, blood pressure increase, increased CO and EF.

Indication: Severe heart failure, cardiogenic shock.

Concentration: Solution 1 mg/ml. Common strength 0.2 mg/ml or 100 µg/ml or 150 µg/ml.

Side effects: Hypotension, increased myocardial oxygen consumption, tachycardia, ventricular extrasystoles, ventricular tachycardia.

Contraindications: Hypovolemia, obstructive aortic or pulmonary valve defect. Caution during acute myocardial infarction.

Morphine

Morphine is well-suited as an analgesic for critically ill patients.

• 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) (over 5-15 minutes)
• Maintenance dose: 1-4 mg/h

Naloxone Hydrochloride (orally)

Naloxone hydrochloride counteracts the inhibitory effect of opioids on intestinal peristalsis by blocking mu receptors in the intestinal wall. Opiates have an inhibitory effect on intestinal peristalsis by releasing acetylcholine in the parasympathetic nervous system, which increases tone, reduces fluid secretion, and decreases intestinal peristalsis. Naloxone is absorbed from the gastrointestinal tract but is metabolized in the liver and does not have a systemic effect, only a local effect in the intestine. Counteracting constipation can reduce the risk of nosocomial pneumonia during intensive care. Can be used simultaneously with other constipation treatments such as Movicol and laxoberaldroppar.

Dosage: 5-8-10 ml x 3 in the tube.

Indication: Opioid-induced constipation.

Concentration: 1 mg/ml (extemporaneous preparation).

Warning: Naloxone should not be given in severe liver failure as it can have a systemic effect with central opioid antagonism due to impaired liver metabolism.

Neostigmine

Neostigmine is an acetylcholinesterase inhibitor that increases acetylcholine concentration, reversing the effect of muscle relaxants, and restoring muscle activity and strength after muscle relaxation during anesthesia. Used to reverse the effects of non-depolarizing muscle relaxants at the end of anesthesia. Neostigmine can also be used to increase intestinal peristalsis in intestinal paralysis and to enhance muscle activity in myasthenia gravis. The administration of neostigmine is preceded by the intravenous administration of an anticholinergic (atropine sulfate or glycopyrronium). Neostigmine is then given in a dose of 0.5-2.5 mg (0.2-1 ml) intravenously. In exceptional cases, doses up to 5 mg (2 ml) may be required. The injection should be given slowly and with respect to effect.

Concentration: 2.5 mg/ml iv

Dosage

30-70 ug/kg. Standard dose for reversal 2.5 mg = 1 ml. If the effect is insufficient, half a standard dose can be repeated (after 10-15 minutes) = 0.5 ml.

Routinely combined with anticholinergics in the form of atropine or glycopyrronium to avoid bradycardia and bronchospasm.

• Neostigmine 2.5 mg + 0.5 mg glycopyrronium (Robinul) (1 ml)
• Neostigmine 2.5 mg (1 ml) + 0.5 mg atropine (1 ml)

Dosage for constipation: 1-2.5 mg iv

Caution

In combination with beta-blockers, bradycardia and hypotension may occur.

Nitroglycerin (Glyceryl nitrate)

Vasodilator. Reduces anginal chest pain. Relaxes smooth muscle in blood vessels and acts as a vasodilator through the formation of NO and cGMP. Reduces venous return to the heart and decreases the heart’s oxygen demand. Improves heart working conditions with less oxygen requirement and prevents myocardial ischemia.

Dosage: In continuous infusion 1-5 ml/h, 20-80 μg/min, 0.1-1.6 μg/kg/min. Initial dose 0.5 μg/kg/min.

Indication: Angina pectoris, myocardial ischemia, heart failure, especially left ventricular failure with pulmonary edema, critical peripheral ischemia.

Concentration: Solution 1 mg/ml.

Side effects: Blood pressure drop, tachycardia, flushing, headache, dizziness, bradycardia also occurs.

Warning: Caution in hypovolemia or tachycardia. May trigger blood pressure drop in mitral stenosis or aortic stenosis. Severe blood pressure drop may occur with concomitant treatment with sildenafil, which can trigger hypotension and myocardial infarction. Concomitant treatment with beta-blockers, vasodilators, calcium antagonists, ACE inhibitors, and antidepressants may potentiate the blood pressure-lowering effect of nitroglycerin.

Contraindications: Hypersensitivity to nitrates and related organic nitrate compounds. Systolic blood pressure below 90 mm Hg. Severe hypotension and hypovolemia.

Nitroprusside sodium (Nitropress/Niprid)

Fast-acting vasodilator and blood pressure reducer

Relaxes smooth muscle in blood vessels and acts as a vasodilator through the formation of NO and cGMP. Reduces venous return to the heart and decreases the heart’s oxygen demand. Improves heart working conditions with less oxygen requirement and prevents myocardial ischemia. Nitroprusside has effects on both arteries and veins, but with a primary effect on veins (though less pronounced than nitroglycerin). The result is “venous pooling” and thereby reduced filling pressures and afterload reduction due to the decreased systemic vascular resistance. The effect sets in after 1-2 minutes and fades away after approximately the same time when stopped.

Dosage: In continuous infusion 1-5 ml/h, 20-80 μg/min, 0.1-1.6 μg/kg/min. Initial dose 0.5 μg/kg/min increase by 0.5-1.0 μg/kg/min every 4-5 minutes until the desired effect is reached or the systolic blood pressure drops to at least 90-95 mmHg systolic, ensuring that urine production is not negatively affected.

Indication: Severe hypertension, aortic dissection, myocardial ischemia, severe heart failure, especially left ventricular failure with pulmonary edema, critical peripheral ischemia.

Concentration: Solution 25 mg/ml diluted to 0.5 mg/ml.

Side effects: Blood pressure drop, tachycardia, flushing, headache, dizziness, bradycardia also occurs.

Warning: Caution in hypovolemia or tachycardia. May trigger blood pressure drop in mitral stenosis or aortic stenosis. Severe blood pressure drop may occur with concomitant treatment with sildenafil, which can trigger hypotension and myocardial infarction. Concomitant treatment with beta-blockers, vasodilators, calcium antagonists, ACE inhibitors, and antidepressants may potentiate the blood pressure-lowering effect of nitroprusside. Liver insufficiency, renal insufficiency. Light-sensitive drug.

There is a (very small) risk of cyanide poisoning during prolonged administration or very high infusion rates, especially in liver insufficiency.

Contraindications: Hypersensitivity to nitrates and related organic nitrate compounds. Systolic blood pressure below 90 mm Hg. Severe hypotension and hypovolemia. Aortic stenosis.

Noradrenaline

Noradrenaline is a sympathomimetic amine. The positive inotropic effect is mainly due to the agonistic effect on the heart’s beta1 receptors, but also on the heart’s alpha1 receptors.

Concentration: Common strength for continuous infusion 0.1 mg/ml. “Double strength” 0.2 mg/ml. Weak strength 0.05 mg/ml.

Receptor activity: α1 +++, β1+++, β2 +. DA-1 none.

Physiological effects: SVR↑, CO+/-, HR↑, BP↑↑,

Indication: Circulatory shock, refractory hypotension, sepsis, anaphylaxis, severe hypotension with vasodilation, cardiogenic shock, severe poisonings.

Side effects: Tachycardia, arrhythmias, renal intestinal hypoperfusion, peripheral ischemia, bowel ischemia, splenic ischemia.

Dosage: 0.01-0.1-(0.5) μg/kg/min = 3-40 ml/h for 70 kg. Common starting dose 0.05 μg/kg/min, adjusted according to blood pressure.

Dose activity: < 0.05 μg/kg/min – usually moderate effect on blood pressure, 0.05- 0.1 μg/kg/min β1 effect, blood pressure increase, > 0.1 μg/kg/min – α1 effect, strong blood pressure increase, vasoconstriction, tachycardia.

Contraindications: Hypertension, hypovolemia, hyperthyroidism, peripheral hypoxia, peripheral vasoconstriction, hyperadrenergic states.

Certainly! Here is the translation of the provided content into English, while maintaining the original format:

Novastan (Argatroban)

Novastan is a coagulation inhibitor by being a direct thrombin inhibitor used to prevent thromboembolic disease in HIT. Argatroban, a synthetic L-arginine derivative, is a direct thrombin inhibitor that reversibly binds to thrombin. Argatroban exerts its anticoagulant effect independently of antithrombin III and inhibits fibrin formation, activation of coagulation factors V, VIII, and XIII, activation of protein C, as well as platelet aggregation.

Dosage: 0.5-2 micrograms/kg/min as a continuous infusion. The usual starting dose is 2 micrograms/kg/min, but several studies have shown that a low dose (0.5 micrograms/kg/min) has been sufficient for intensive care patients. The target is an APTT prolonged to 1.5-3 times the patient’s initial APTT value, but always below 100 seconds.

Indication: Thromboprophylaxis in Heparin-induced thrombocytopenia (HIT).

Concentration: Concentrate of 100 mg/ml diluted to 1 mg/ml (250 mg (2.5 ml) diluted in 250 ml NaCl 9mg/ml or 250 ml Glucose 5%).

Warning: Contraindicated in active bleeding. Caution in liver failure.

Octreotide (Sandostatin®)

Octreotide is a synthetic octapeptide analog of the naturally occurring somatostatin with similar pharmacological effects but a significantly longer duration of effect.

Dosage: Initially, 50 μg 1-2 times daily as a subcutaneous injection. If needed, the dose can be gradually increased to 200 μg 3 times daily. Can be administered intravenously by infusion for the treatment of bleeding esophageal varices, 25 μg per hour.

Indication: Carcinoid syndrome and VIP-producing tumors. Bleeding esophageal varices.

Side effects: Bradycardia. Reduced levels of vitamin B12. Gallstones. Cholecystitis.

Concentration: 50 μg/ml, 100 μg/ml, 200 μg/ml, 500 μg/ml.

Warning: Patients with insulin-dependent diabetes may have a reduced need for insulin.

Phentolamine (Regitine®)

Phentolamine (Regitine) is an adrenergic receptor antagonist and an effective antidote for the extravasation of norepinephrine.

Indication: Accidental extravasation of norepinephrine and other adrenergic agents.

Accidental extravasation of adrenergic medications, especially norepinephrine during peripheral administration in a peripheral venous catheter (PVC), can cause pronounced local vasospasm, potentially leading to ischemia, blistering, ulceration, and necrosis. If extravasation is suspected, for example, if the skin turns white, immediately stop the infusion and contact the responsible anesthesiologist.

There are two treatment options that can be used together or separately:

1. Regional blockade (plexus, epidural) with local anesthesia, preferably via a catheter.
2. Local infiltration with phentolamine.

It is available in various antidote storage facilities. To prevent scabbing and necrosis in areas where extravasation has occurred, it is recommended that the area be infiltrated as soon as possible:

Preparation:

• Mix: Regitine/Phentolamine (10 mg/ml) 1 ml; 10 mg with NaCl (9 mg/ml) 14 ml for a total of 15 ml.
• Concentration: 1 mg/ml.
• Injection solution: 10 mg/ml 2 x 5 x 1 ml, cold storage required. A license is required.

Dosage:

Generously infiltrate subcutaneously in a fan-shaped pattern, using a fine injection needle in the cold, hard, and pale area with 10 – 15 ml of the diluted solution (adult patient).

Phentolamine usually causes immediate and visible local hyperemia in the area. Be aware that the medication can also be absorbed systemically and may cause hypotension. In rare cases, surgical revision of the injury may be necessary.

Phenylephrine (Metaoxedrine)

Phenylephrine is a sympathomimetic substituted phenethylamine. Pure alpha-agonist. Causes vasoconstriction and blood pressure elevation. Decreased cardiac output (CO), increased diastolic blood pressure, and mean arterial pressure (MAP).

Receptor activity: α₁ +++, β₁ zero, β₂ zero, DA-₁ zero.

Physiological effects: Increased SVR, decreased CO, decreased HR, increased BP, reflex bradycardia.

Indication: Hypotension, vasodilation, blood pressure drop after spinal anesthesia and epidural anesthesia.

Side effects: Bradycardia, heart failure, pulmonary edema.

Concentration: Ready-to-use solution 0.1 mg/ml. Common strength is 0.1 mg/ml. Also available in the strength of 10.0 mg/ml.

Dosage: 0.1-0.2 mg IV. Common starting dose 0.1 mg IV, adjusted according to blood pressure. Phenylephrine is most often given in repeated bolus doses but can also be given in continuous infusion at a strength of 0.1 mg/ml. Common dosage is 0.05-0.5 μg/kg/min = about 3 – 20 ml/h for 70 kg.

Dosage activity: < 0.3 mg – usually moderate effect on blood pressure, unchanged CO, > 0.5 mg decreased CO, vasoconstriction.

Physostigmine (Anticholium)

Antidote to the central nervous effects of anticholinergic drugs. Reversible cholinesterase inhibitor. Physostigmine crosses the blood-brain barrier, unlike neostigmine, and can reverse central anticholinergic effects of drugs such as confusion and agitation. Other anticholinergic symptoms include tachycardia, high blood pressure, dilated pupils, red warm and dry skin, urinary retention.

Physostigmine has a half-life of 30-60 minutes and may need to be given repeatedly.

Indication: Overdose or poisoning with anticholinergic drugs. Anticholinergic syndrome. Nonspecific treatment for some of Baclofen’s effects.

Concentration: 5 ml ampoule with 2 mg physostigmine (0.4 mg/ml).

Dosage: adult 1-2 mg intravenously, slow administration about 0.2 mg/min. Children: 0.02 mg/kg intravenously. Administer with caution due to the risk of inducing epileptic seizures and bradycardia.

Propofol (Diprivan®, Propolipid®, Recofol®, Propofol)

Intravenous anesthetic and sedative. Propofol is used for the sedation of ventilated patients over 16 years in the intensive care unit. Propofol can also be used with caution in non-ventilated patients for sedation. Propofol (2,6-diisopropylphenol) is a substituted phenol that induces anesthesia when administered intravenously. The mechanism of action of propofol is unknown, but it is likely that the effect is exerted via a non-specific membrane binding of the substance.

Dosage: 1-3 mg/kg/hour (2-15 ml/hour, 20 mg/ml). TIVA mode.

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

Concentration: 20 mg/ml, 10 mg/ml.

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

Protamin sulfate (Protamin)

Antidote to heparin. Protamin sulfate contains basic peptide sulfates that complex bind heparin. For low molecular weight heparin (LMWH), anti-IIa activity is fully neutralized, and anti-Xa activity is partially neutralized. The degree of neutralization varies between different LMWH. The effect is almost immediate.

Dosage: Bolus dose of 5 ml (50 mg) given intravenously over 10 minutes neutralizes approximately 7,000 IU of heparin. One ml of protamine neutralizes 1400 IU of heparin. If possible, APTT or ACT (activate clotting time) is checked immediately before and 15 minutes after administration.

Indication: Overdose and severe bleeding with heparin or LMWH. To reverse the heparin effect before emergency surgery. To neutralize the heparin effect in connection with treatment in a heart-lung machine.

Concentration: Injection solution 1400 IU/mL.

Side effects: Excess can cause bleeding and APTT prolongation.

Warning: Hypersensitivity to protamine or fish allergy. Thrombocytopenia after the heart-lung machine may be aggravated.

Prothrombin complex concentrate (Ocplex)

Hemostatic agent. Coagulation factors II, VII, IX, and X, synthesized in the liver with the help of vitamin K.

Dosage: The dose is determined by INR before treatment and the target INR. Typically, 2-3000 IU Ocplex is given. The single dose should not exceed 3,000 IU (120 ml Ocplex).

Indication: Major bleeding, bleeding in liver failure. Treatment of bleeding and perioperative bleeding prophylaxis in acquired deficiency of prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists (Warfarin) or in overdose of Warfarin, when rapid correction of the deficiency is required. Correction of elevated PK/INR.

Concentration: Powder for solution 500 IU.

Side effects: Thromboembolic events including myocardial infarction and pulmonary embolism. Lack of effect.

Warning: Patients receiving a vitamin K antagonist may have an underlying hypercoagulable state, and infusion of prothrombin complex concentrate may exacerbate this. Replacement therapy may, in rare cases (>0.01% and <0.1%), lead to the formation of circulating antibodies that inhibit one or more of the human prothrombin complex factors.

Contraindications: Known allergy to heparin or history of heparin-induced thrombocytopenia.

Racemic adrenaline (Racepinephrine)

Synthetic catecholamine with sympathomimetic and mucosal decongestant effects for inhalation treatment of subglottic edema. Adrenaline stimulates alpha-1, alpha-2, beta-1, and beta-2 receptors, mainly beta-2 receptors. Adrenaline causes relaxation of smooth muscle and counteracts bronchospasm and mucosal swelling. Racepinephrine can be used in subglottic edema, especially in children up to 20 kg, but it can also be tried in adults, e.g., after prolonged intubation with stridorous breathing. Treatment with Racepinephrine should not delay other treatments for upper airway obstruction, such as intubation or emergency tracheotomy. The treatment has an effect within a few minutes with a duration of about 30 minutes.

Dosage: Racepinephrine 22.5 mg/ml diluted in a nebulizer with NaCl 9 mg/ml to a volume of at least 2 ml. Half the amount is inhaled first. Then wait 10 minutes under control of the child’s pulse and respiratory rate. The pulse rate should not become too high, normally up to 120 beats/min is accepted. Then start the second half of the dose. If oxygen saturation worsens, consider emergency intubation.

Alternative: Adrenaline injection solution 1 mg/ml can be inhaled, up to 5 mg (5 ml). Can be repeated if necessary, but no sooner than 2 hours after the first treatment.

Indication: Acute subglottic laryngitis, pseudocroup, croup, bronchospasm, stridorous breathing.

Concentration: Inhalation solution 22.5 mg/ml (2.25%).

Warning: May cause tachycardia, high blood pressure, cardiac arrhythmias, anxiety, tremor. Caution with pulse over 120.

Remodulin (Treprostinil)

Treprostinil is a prostacyclin analog. The main pharmacological effects of prostacyclin (PGI2) include significant vasodilation of the pulmonary vascular bed and systemic circulation, inhibition of platelet aggregation, and antiproliferative effects. It exerts a direct vasodilating effect on the pulmonary and systemic circulation and inhibits platelet aggregation.

In animals, the vasodilatory effect reduces the afterload in the left and right ventricles and increases cardiac output and stroke volume. The effect of treprostinil on heart rate in animals is dose-dependent. No major effects have been observed on AV conduction.

Dosage: The recommended initial infusion rate is 1.25 ng/kg/min. If the initial dose is not well tolerated, the infusion rate can be reduced to 0.625 ng/kg/min. The infusion rate should be increased gradually under medical supervision by 1.25 ng/kg/min per week during the first four weeks of treatment and then by 2.5 ng/kg/min per week.

Indication: Pulmonary hypertension, right ventricular failure.

Concentration: Each ml contains 1 mg, 2.5 mg, 5 mg, or 10 mg treprostinil as treprostinil sodium. Administered as an intravenous infusion through a central line.

Side effects: Hypotension, vasodilation, prolonged bleeding time, jaw pain, headache, leg pain, diarrhea, nausea. All are dose-dependent.

Warning: Side effects such as chest rigidity, breathing difficulties, irregular heartbeat, skin bleeding, and hematuria.

Remifentanil (Ultiva)

Intravenous short-acting analgesic and sedative. Remifentanil is a selective, highly potent μ-opioid agonist with rapid onset and short duration of action. Remifentanil is an esterase-metabolized opioid, metabolized by non-specific blood and tissue esterases.

Indication

Pain relief and sedation in mechanically ventilated patients in intensive care who are 18 years and older. Used as an analgesic during induction and/or maintenance of general anesthesia during assisted ventilation in surgical procedures, including anesthesia during cardiac surgery.

Dosage

Maintenance dose for sedation in ICU is 0.05-0.25 μg/kg/min.

After administering recommended doses of remifentanil, the effective half-life is 3-10 minutes. The average clearance of remifentanil in healthy young adults is 40 ml/min/kg, central distribution volume is 100 ml/kg, and distribution volume at steady state is 350 ml/kg.

Remifentanil reduces the need for hypnotics necessary to maintain anesthesia, 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.

Solution 50 μg/ml. The recommended dilution for sedation is 50 μg/ml for adults and 20 μg/ml for children ≥1 year.

Remifentanil and Hyperalgesia

Hyperalgesia is defined as increased pain intensity at a constant pain stimulus. Hyperalgesia can occur after administration of remifentanil. This hyperalgesia may be due to two mechanisms: opioid-induced hyperalgesia and the induction of acute opioid tolerance. Studies show increased morphine consumption postoperatively after anesthesia with high doses of remifentanil and no blocks are placed, compared to similar surgeries where another anesthesia technique is used. This hyperalgesia can be partially counteracted by using gabapentin in premedication or by giving ketamine as an intraoperative supplement in low doses. A disadvantage of gabapentin is that patients can become very tired.

Remimazolam (Byfavo)

Remimazolam is a short-acting sedative benzodiazepine. Remimazolam is indicated for procedure-related sedation in adults. Remimazolam is a potent sedative intravenous drug that requires careful titration and slow administration. The patient’s physical status, age, and other medications must be considered.

Remimazolam has a rapid onset and the sedation subsides quickly. The effect sets in around 1-2 minutes after injection. The maximum effect is reached after 3 – 3.5 minutes. Patients wake up fully 12-14 minutes after the last dose of remimazolam.

The distribution volume at steady state is 0.9 l/kg. Remimazolam is 90% bound to plasma proteins, mainly albumin. In healthy volunteers, the elimination half-life of remimazolam is between 7 and 10 minutes. The half-life and effect are significantly prolonged in severe liver disease.

Indication: Sedation in connection with diagnostic examinations or therapeutic interventions, e.g., catheterizations or endovascular procedures.

Concentration: Solution: 2.5 mg/ml. (20 mg in 8 ml). Usually given intravenously.

Dosage

Sedation before procedures with opioid in adults < 65 years

Induction: Administer opioid and wait 1–2 minutes.

Starting dose: Injection: 5 mg (2 ml) in 1 minute. Wait 2 minutes. The remimazolam dose should be titrated individually to the effective dose that provides the desired sedation depth and minimizes side effects. Additional doses may be administered as needed to induce or maintain the desired sedation level. At least 2 minutes should elapse before any additional dose is administered to allow a full assessment of the sedative effect.

Maintenance/titration: Injection: 2.5 mg (1 ml) in 15 seconds.

The highest total dose administered in clinical trials was 33 mg.

Sedation before procedures with opioid in adults ≥ 65 years and/or with ASA-PS III–IV and/or body weight < 50 kg

Induction: Administer opioid and wait 1–2 minutes.

Starting dose: 2.5–5 mg (1–2 ml) in 1 minute. Wait 2 minutes.

Maintenance/titration: Injection: 1.25–2.5 mg (0.5–1 ml) in 15 seconds.

The highest total dose administered in clinical trials was 17.5 mg.

Sedation before procedures, without opioid in adults < 65 years

Induction injection: 7 mg (2.8 ml) in 1 minute. Wait 2 minutes.

Maintenance/titration: Injection: 2.5 mg (1 ml) in 15 seconds.

The highest total dose administered in clinical trials was 33 mg.

Sedation before procedures, without opioid in adults ≥ 65 years and/or with ASA-PS^# III–IV and/or body weight < 50 kg

Induction injection: 2.5–5 mg (1–2 ml) in 1 minute. Wait 2 minutes.

Maintenance/titration: Injection: 1.25–2.5 mg (0.5–1 ml) in 15 seconds.

The highest total dose administered in clinical trials was 17.5 mg.

In patients with hypovolemia, vasoconstriction, or hypothermia, the maintenance dose should be reduced. Sedation levels should be regularly assessed.

Side effects: Respiratory failure, bradycardia, hypotension.

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

Contraindications: Hypersensitivity to the active substance or other benzodiazepines. Unstable myasthenia gravis and other neuromuscular diseases.

Rituximab (Mabthera)

Mediates B-cell lysis.

Rituximab specifically binds to the transmembrane antigen, CD-20, a non-glycosylated phosphoprotein, located on pre-B and mature B lymphocytes. By binding to the CD20 antigen on B lymphocytes, rituximab has also been shown to induce cell death via apoptosis.

Dosage: 375 mg/m2 body surface area as a single dose. The recommended initial infusion rate is 50 mg/hour. After the first 30 minutes, the rate can gradually be increased by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour.

Concentration: Concentrate 100 mg, 500 mg.

Indication: Prophylaxis against rejection and treatment of rejection after organ transplantation. Non-Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), rheumatoid arthritis.

Side effects: Hypotension, bronchospasm, serious infections including sepsis and pneumonia, hepatitis B reactivation.

Warning: Acute severe infections, severe immunosuppression. Risk of developing progressive multifocal leukoencephalopathy (PML). Risk of allergic reactions exists during the infusion of all protein products. Fifteen minutes before Mabthera injection, give: Solu-Medrol 250 mg i.v. and Tavegyl 2 mg i.v. During Mabthera treatment, all patients should receive steroid protection. In case of rejection and previous treatment with murine products (OKT3, Simulect), there is an additional risk of cytokine release syndrome, so extra careful monitoring of the patient is recommended.

Rocuronium (Esmeron®)

Non-depolarizing muscle relaxant. Adjuvant to general anesthesia to facilitate endotracheal intubation and to achieve skeletal muscle relaxation during surgical procedures of medium to long duration. Usually, patients are muscle relaxed during abdominal surgery (open or laparoscopic), orthopedic surgery, and other surgeries where the patient must remain completely still. To facilitate manual or mechanical ventilation of the anesthetized patient.

Intubation dose: 0.6 mg/kg IV (1.0 mg/kg for RSI); 40-50 mg to a normal-weight adult, 10 mg/ml = 4-5 ml.

Standard dose: 50 mg. Maintenance 0.15 mg/kg, 10-20 mg per occasion. Administered every 20 to 60 minutes during general anesthesia.

Caution: Previous reaction to muscle relaxants, myasthenia gravis, or similar neuromuscular disease.

Reversal: Robinul-Neostigmine 1-2 ml IV (neostigmine 2.5-5 mg + glycopyrronium 0.5-1 mg) or Atropine 1 mg + Neostigmine 2.5 mg IV.

Sildenafil (Revatio)

Sildenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), the enzyme responsible for the breakdown of cGMP. Sildenafil thereby increases cGMP in the smooth muscle cells of the pulmonary vessels, resulting in vasodilation.

Indication: Primary pulmonary hypertension (PPH).

Dosage: 20 mg x 2-3 daily orally.

Concentration: Tablet 20 mg. Injection solution 0.8 mg/ml. Oral suspension 10 mg/ml.

Side effects: Headache, flushing, hypotension, pain in extremities, peripheral edema, blurred vision, nasal congestion, night sweats.

Warning: Caution with hypotension, fluid depletion, left ventricular outflow obstruction, or autonomic dysfunction.

Steroid Scheme for Adults (Cortisone Scheme)

Dosage of Betapred is individual, weight-based, and determined and prescribed by the operator. Betapred scheme for children is recommended for children < 30 kg. For children weighing 30-60 kg, half of the adult scheme is recommended. Children over 60 kg are considered adults and recommended the adult scheme.

Succamethonium – Succinylcholine (Celocurin®)

Depolarizing muscle relaxant. Ultra-short-acting agent with very rapid onset. Used to quickly achieve muscle relaxation and airway control. For intravenous use only. Adjuvant to general anesthesia to facilitate endotracheal intubation and achieve skeletal muscle relaxation during short-duration surgical procedures. To facilitate manual ventilation of the anesthetized patient. Onset within 60-90 seconds. Used to create optimal intubation conditions quickly.

Intubation dose: 1-1.5 mg/kg IV = 25-100 mg IV (may pre-treat with atropine), 50 mg/ml solution.

Standard dose: 75 mg IV, 50-100 mg, 1-2 ml IV.

Caution: Hyperkalemia, recent burn injury, malignant hyperthermia, muscle diseases, major tissue injuries, bradycardia.

Sufentanil (Sufenta®)

As an analgesic component in balanced general anesthesia induced and maintained with multiple anesthetics:

Initial dose – slow IV bolus or infusion over 2–10 minutes: 0.5–2 μg sufentanil/kg body weight. The duration of effect is dose-dependent. The duration of effect for a dose of 0.5 μg sufentanil/kg body weight is approximately 50 minutes.

Maintenance dose – administered intravenously upon signs of superficial anesthesia: 10-50 μg sufentanil (approximately 0.15–0.7 μg/kg body weight).

Awakening phase – during this phase, the dose must be reduced very slowly.

As an anesthetic for induction/maintenance of anesthesia:

Initial dose – slow IV injection or short infusion over 2–10 minutes: 7-20 μg sufentanil/kg body weight.

Maintenance dose – administered intravenously upon signs of superficial anesthesia: 25-50 μg sufentanil (approximately 0.36–0.7 μg/kg body weight). Maintenance doses of 25-50 μg sufentanil are usually sufficient to maintain stable cardiovascular status during anesthesia.

Sugammadex (Bridion)

Antidote to non-depolarizing muscle relaxants, for intravenous use. Sugammadex is a derivative of gamma-cyclodextrin. Sugammadex forms a complex with the neuromuscular blocking agents rocuronium and vecuronium in plasma, thereby reducing the amount of muscle relaxant that can bind to the nicotinic receptor in the neuromuscular junction.

Dosage: For normal reversal 4 mg/kg, which gives 280 mg (2.8 ml) to a 70 kg patient. For children and adolescents, only 2 mg/kg is given, which gives 80 mg (0.8 ml) to a 40 kg child.

Indication: Reversal of the muscle relaxants rocuronium (Esmeron) and vecuronium (Norcuron). Effect usually occurs within 2 minutes with nearly complete recovery of muscle strength.

Concentration: Solution 100 mg/ml (2 or 5 ml ampoules).

Side effects: Hypersensitivity, anesthesia complications such as too rapid restoration of muscle tone during surgery.

Warning: Risk of rapid restoration of muscle tone during surgery, which can complicate the surgical work. Anaphylactic reactions may occur.

Tacrolimus (Prograf)

Tacrolimus is a highly potent immunosuppressant and has been shown to be effective both in vitro and in vivo. Tacrolimus specifically inhibits the formation of cytotoxic lymphocytes, which mainly cause transplant rejection. Tacrolimus suppresses the activation of T-lymphocytes and T-helper cell-dependent proliferation of B-cells as well as the formation of lymphokines such as interleukin-2, 3, and gamma-interferon, and the expression of the interleukin-2 receptor.

Dosage: Oral treatment with Prograf should be initiated at 0.10 – 0.20 mg/kg/day, given as two daily doses. Administration should begin approximately 12 hours after surgery. If the dose cannot be given orally due to the patient’s condition, treatment should be initiated with intravenous administration of 0.01–0.05 mg/kg/day as a continuous intravenous infusion. Most patients can be adequately treated if tacrolimus trough levels are kept below 20 ng/ml. In clinical use, trough levels in whole blood have ranged from 5-20 ng/ml in liver transplant patients and 10-20 ng/ml in kidney and heart transplant patients during the period immediately after transplantation.

Indication: Treatment of transplant rejection that is resistant to treatment with other immunosuppressive drugs. Prophylaxis against transplant rejection in liver, kidney, and heart transplant patients.

Concentration: Injection solution 5 mg/ml. Capsules 0.5, 1, 2 mg.

Side effects: Left ventricular hypertrophy and/or septal hypertrophy, reported as cardiomyopathy, have been reported in rare cases. Development of EBV-associated lymphoproliferative disorders and posterior reversible encephalopathy syndrome (PRES).

Concentration: Injection solution 5 mg/ml. Administered as an intravenous infusion in a central line.

Warning: Hypersensitivity to tacrolimus or other macrolides.

Thiopentone (Pentocur, Pentothal)

Pentothal (“Pento”) is a rapid-acting intravenous anesthetic, barbituric acid derivative. Hypnosis occurs within 30-40 seconds. Physiological effects: BP↓, CO↓, decreased ejection fraction (EF), decreased contractility, blood pressure drop, unchanged or decreased SVR. Anticonvulsant.

Dosage: For manual induction 4-6 mg/kg body weight slowly intravenously, usually a test dose is given first of 25-50 mg. Lower doses for elderly and patients with hypotension, liver failure, or compromised hemodynamics. In continuous intravenous infusion 2-4 mg/kg/h (2-10 ml/h) for the treatment of elevated intracranial pressure, adjusted based on pulse and blood pressure, 1-4 ml/h. Can be given in bolus doses of 4-8 mg/kg (40-300 mg) at a rate of 50 mg/minute depending on circulatory status.

Indication: For induction of general anesthesia, especially in emergency cesarean section or neuroanesthesia. For the treatment of general convulsions, status epilepticus, or elevated intracranial pressure.

Concentration: Powder, usually diluted to a solution of 25 mg/ml (2.5%).

Concentration for infusion: Common strength 25 mg/ml (alt. 12.5 mg/ml). For continuous infusion, the drug should be given in a central venous catheter (CVC).

Side effects: Blood pressure drop, somnolence, prolonged awakening, respiratory depression, asystole, bronchospasm, laryngospasm, sleep disturbances. Thiopental can cause dependency. Thiopental crosses the placenta.

Contraindications: Bronchospasm, severe hypotension, severe heart failure, Takotsubo cardiomyopathy, hypovolemia, mechanical obstruction in the left ventricle, porphyria, asthma. Caution in renal insufficiency or liver insufficiency. Caution in concomitant treatment with other antiarrhythmics, digitalis, or amiodarone.

Tranexamic Acid (Cyklokapron)

Fibrinolysis inhibitor. Tranexamic acid inhibits fibrinolysis by preventing the activation of plasminogen to plasmin. Tranexamic acid does not cause thrombosis but inhibits the dissolution of existing thrombi.

Dosage: Initially, a slow (10 minutes) intravenous injection of 1-2 g IV is given, which can be repeated after 4-6 hours. Infusion can be given at a dose of 70-700 mg/hour. Cyklokapron can be applied locally on mucous membranes, in the oral cavity, and in the nose.

Indication: For surgery and bleeding in patients with increased bleeding tendency. For surgeries with increased fibrinolysis, such as mucous membrane surgeries, mammoplasty, thoracic and liver surgery, and prostate surgery. For surgery in patients with increased bleeding risk, such as known platelet defects, von Willebrand’s disease, and hemophilia. It can be tried in cases of major bleeding associated with severe trauma.

Concentration: Injection solution 100 mg/mL.

Side effects: In DIC and microthrombotic syndromes, tranexamic acid may reduce the dissolution of fibrin in the microcirculation, thereby increasing the risk of organ failure.

Contraindications: Cyklokapron should be avoided for the first six months after acute thrombosis. In cases of severe major bleeding, single doses of tranexamic acid can be given, but treatment for several days should be avoided. Bleeding in the urinary tract is a contraindication due to the risk of obstructive clot formation.

Vasopressin

Vasopressin is an antidiuretic hormone that regulates water reabsorption in the renal distal tubules. It regulates water balance, increases urine osmolarity, and increases peripheral vasoconstriction and blood pressure.

Receptor activity: V₂+++, α₁-none, β₁-none, β₂-none, DA-₁ none.

Physiological effects: SVR↑↑, CO↓, HR↓, BP↑↑.

Indication: Sepsis, adjunctive treatment to vasopressor therapy with norepinephrine in septic shock.

Side effects: Bradycardia, vasoconstriction, pulmonary edema, arrhythmias, renal intestinal hypoperfusion, peripheral ischemia, intestinal ischemia.

Concentration: Common strength 0.4 IU/ml.

Dosage: 0.01-0.06 IU/min = 2-4 ml/h for 70 kg. Common starting dose 0.04 IU/min, adjusted according to blood pressure. Higher doses in hemorrhagic shock than in sepsis treatment.

Dose-activity: < 0.02 IU/min slight blood pressure increase, > 0.04 IU/min – α₁-effect, significant blood pressure increase, vasoconstriction.

Contraindications: Hypertension, hypovolemia, hyperthyroidism, peripheral hypoxia, peripheral vasoconstriction, hyperadrenergic states.

Vitamin K (Phytomenadione – Konakion®)

Vitamin K is required for the vitamin K-dependent coagulation factors II, VII, IX, X, as well as proteins C and S to be synthesized into active coagulation factors.

Dosage: In acute bleeding conditions, administer 10-20 mg Konakion IV. The effect begins to appear after 4-6 hours. The injection is given

slowly over at least 30 seconds.

Indication: Elevated PK (INR) with bleeding risk or ongoing bleeding. To expedite lowering of PK (INR) before surgery in patients on coumarin drugs (Waran). Malnutrition with liver or intestinal disease.

Concentration: Injection solution 10 mg/ml.

Side effects: Thromboembolic complications. Exercise caution in patients with an increased risk of thromboembolism or mechanical heart valve.

Warning: Injection of Konakion can cause a drop in blood pressure, so caution must be exercised when treating patients in shock.