[Sedation and analgesia in intensive therapy].

BACKGROUND

In the operating room, anaesthetist must provide unconsciousness, analgesia and muscular relaxation. In intensive therapy (IT), the rules are different and not every patient requires sedation, but almost every patient needs analgesia. The patient who is alert, calm and comfortable despite the presence of tubes and cannulas in the nose, mouth, radial artery, central vein, urethra, surgical wounds, pleural space etc. does not need any sedation. However, sedation and analgesia are clinically inseparable. If mechanical ventilation is not well controlled, muscular relaxants must be prescribed. There are a lot of trials in formulating an ideal sedative/analgesic regimen for each individual patient.

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It is not rare that IT patients are oversedated or undersedated. Undersedation is followed by anxiety, pain, hypertension, tachycardia. The most important effect of oversedation is respiratory depression, hypotension, bradycardia, CNS depression, renal dysfunction, immunological depression.

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Benzodiazepines are among the most widely used drugs in IT. They have sedative, hypnotic, anxyolytic, amnestic, anticonvulsant and myorelaxant effects. Prolonged continuous infusion of benzodiazepines ought to be escaped because of prolonged sedation, accumulation and presence of pharmacologically active metabolites. They have proved to be safe, although they can depress ventilation. Since benzodiazepines are not analgesics, the combined use of an opioid and benzodiazepines is necessary. Many different benzodiazepines are available, but the agents most commonly used in critically ill are: midazolam, diazepam and lorazepam. Midazolam is the most extensively used.

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The most frequently used drugs in the group of the butyrophenones are droperidol and haloperidol. Although these drugs are chemically unrelated to the phenothiazines they have similar actions.

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Opioids have the main place in management of analgesia in IT, especially in patients on mechanical ventilation. In management of postoperative analgesia, epidural route has advantage because less drug is necessary and cardiovascular and respiratory effects are minimal. Morphine is a standard opioid to which all others are compared. Intravenous bolus dose is 1-5 mg (0.1-0.15 mg/kg) or continuous infusion 2-15 mg/h. Hypotensive effect is caused by direct vasodilation and relief of histamine. Morphine has long elimination half-time and there is a danger of acummulation after prolonged administration. Morphine metabolites are pharmacologically active and renally eliminated. Prolonged i.v. infusion needs careful titration because of tolerance. Pethidine is less potent than morphine, usually given as a bolus dose (10 mg) or a continuous i.v. infusion (10-20 mg/h). Other opioid agents used in IT are: fentanil, alfentanil, sufentanil. Non-steroidal anti-inflammatory drugs (NSAID-s) are: aspirin, ibuprofen, ketoprofen, diclofenac, ketorolac. NSAID-s may have an opioid sparing effect and be of particular benefit for the relief of pain from bones and joints. They interfere with the metabolism at the site of the sensory nerve terminals. Several chemicals are released locally in response to tissue injury. Arachidonic acid is produced from damaged cell membranes. One series reactions is mediated by the enzyme cyclo-oxygenase (COX) and results in the formation of prostaglandins, prostacyclins and thromboxane. The cyclo-oxygenase pathway is inhibited by NSAID-s. These analgesics, besides peripherally, also work centrally by mechanisms which are not in connection with COX inhibition.

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There are two barbiturates in use: thiopentone and pentobarbital. Although the main effect is hypnosis, the most important is anticonvulsant effect. Thiopentone is an agent for cerebral protection. Barbiturates have not achieved popularity in IT because of prolonged elimination and slow recov