Sedation, analgesia and muscle relaxation in the intensive care unit

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Chapter 81 Sedation, analgesia and muscle relaxation in the intensive care unit

Peter V. van Heerden

Despite the widespread use of sedative and analgesic agents in the intensive care unit (ICU), the goals of sedation and analgesia are not well-established. Indications for the use of sedative agents include:

• to enable the critically ill patient to tolerate invasive and uncomfortable monitoring and treatment procedures

• to reduce oxygen consumption ¹ by reducing patient arousal and activity

• to promote amnesia for events in the ICU

Sedatives may also be used as specific treatment for conditions such as epilepsy or tetanus. The delirious patient may require sedation to maintain safety of the patient and carers.

Combinations of opioids and benzodiazepines are commonly used to provide ‘sedation’ in the ICU. High doses of opioid analgesics may result in significant sedation in their own right and are synergistic with sedative agents such as benzodiazepines. The distinction between sedation and analgesia is therefore blurred, and makes the definition and attainment of clear sedation goals elusive.

Skilled use of analgesics in the modern ICU ensures that critically ill patients should no longer suffer pain. Pain management relies largely on the use of opioid analgesics, together with regional anaesthetic techniques. Poor management of sedation and analgesia in the critically ill patient may contribute to ongoing psychological morbidity, such as posttraumatic stress disorder.

SEDATION

Sedation of patients in the ICU is an integral part care and compassion for the critically ill patient.

Sedative agents are used in an attempt to:

• allay anxiety over the patient’s own illness, the welfare of relatives or the risk of death

• ensure adequate rest

• reduce the impact of unpleasant sensations, such as thirst

• reduce the distress of invasive treatment and monitoring, such as endotracheal intubation

• blunt awareness of the environment over which the patient has very little control and in which he/she may be unable to communicate

Attention to such details as avoiding potentially distressing situations, where possible, allowing adequate access to caring visitors maintaining of adequate communication with the patient and a positive outlook by the carers will satisfy many of these goals. Small comforts, such as ice chips by mouth, a comfortable mattress or relaxation audio tapes all help this process.

LEVEL OF SEDATION

The level of sedation required will vary, depending on the indication, e.g. heavy sedation may be necessary during the control of status epilepticus, while a much lower level of sedation will be required to tolerate endotracheal intubation. Modern modes of mechanical ventilation do not demand heavy sedation in order to be comfortably tolerated. The aim of sedation should be clear to the treating team and the desired level of sedation should be determined and documented. Once sedation is instituted, the level of sedation should be regularly assessed. Protocol-based therapy reduces drug costs and enhances the quality of sedation and analgesia.² Failure to follow such a protocolised approach can result in significant problems, such as:³

• ‘oversedation’ with an increased risk of nosocomial pneumonia

• the need for more frequent neurological assessments including computed axial tomography (CT) scans

• prolonged stay in the ICU

• an increased incidence of psychological problems, such as posttraumatic stress disorder and depression

Level of sedation may be assessed by means of a number of measurement tools including:

• Scoring systems such as the Ramsay scale (see Table 81.1), which is a six-point scale that ranges from anxious and agitated (level 1) to unresponsive (level 6), judged in response to a standardized stimulus (loud auditory stimulus or glabellar tap).³ This scale has good interrater reliability and provides a numerical score, suitable for charting on the ICU observation chart and for descriptive purposes.

• Electroencephalography (EEG), which may be either ‘raw’ or ‘processed’ and is able to provide a measure of cerebral activity. This monitor is more suitable for assessing depth of anaesthesia and may be difficult to interpret in the encephalopathic patient. Newer, easy-to-use devices using integrated EEG are now appearing but their efficacy and role in the ICU have yet to be established. Use is also limited by practical considerations, such as interference due to movement artefact. To date these monitors have not enjoyed widespread use in the ICU, but may be useful for specific indications such as ensuring an isoelectric EEG trace in patients being treated for intracranial hypertension.

• Visual analogue scales, which are more suited to the assessment of pain (see below), or for use as a research tool.

• Evoked potentials.

Table 81.1 Ramsay scale

Level	Response
Awake levels
1	Patient anxious and agitated or restless or both
2	Patient cooperative, orientated and tranquil
3	Patient responds to commands only
Asleep levels
4	Brisk response to a light glabellar tap or loud auditory stimulus
5	Sluggish response to a light glabellar tap or loud auditory stimulus
6	No response to a light glabellar tap or loud auditory stimulus

Level of sedation may also be assessed by monitoring physiological parameters for signs of distress. A ‘drug free’ period every day, when sedative agents are completely withdrawn, is an excellent means of assessing level of sedation ⁴ – by taking note of the time for a patient to either wake up or rise to a predetermined level on the Ramsay scale.

SEDATIVE AGENTS USED IN THE ICU

BENZODIAZEPINES

Benzodiazepines (BZAs), as a class, are probably the most widely used sedatives in ICUs. These agents provide hypnosis, amnesia and anxiolysis. They do not provide analgesia. BZAs are good anticonvulsant drugs and also provide some muscle relaxation. They act via BZA receptors, which are closely associated with GABA_A receptors, resulting in intracellular influx of chloride when activated. These drugs may be given by mouth (PO), per rectum (PR) or intravenously (i.v.). Most commonly in the ICU they are administered by intermittent or continuous i.v. infusion, e.g. midazolam in 1 mg/ml dilution, titrated to effect.

Dosage of these agents is by titration and may vary widely depending on factors such as:

• prior exposure to BZA (increased tolerance)

• age and physiological reserve

• volume status (hypovolaemic patients are more sensitive)

• renal and hepatic dysfunction

• co-administered drugs (whether BZA is combined with an opioid)

• history of alcohol consumption (increased tolerance)

Although some BZAs (e.g. midazolam) are reported to be short-acting, water-soluble agents, there is still potential for accumulation of both parent compound and active metabolites in patients with hepatic and renal dysfunction. This may result in prolonged sedation and increased length of mechanical ventilation and ICU stay. In the critically ill, there may be extensive derangement of the pharmacokinetic profiles of BZAs. There is therefore some difficulty in predetermining suitable dosages of these agents. Typically, midazolam in doses of 0.02–0.2 mg/kg per hour may be suitable, with the level titrated to individual response. Longer acting agents, such as diazepam, may be given by intermittent i.v. injection, e.g. diazepam 5–10 mg i.v., as necessary.

BZAs are often combined with opioids in a compound ‘sedative’ infusion. This allows lower doses of BZA to be used, while capitalising on the opioid effects of respiratory and cough suppression, to facilitate mechanical ventilation.

Flumazenil, the specific BZA antagonist, may be used to reverse the effect of BZAs to reduce unwanted acute side-effects, such as severe hypotension or respiratory depression, or to allow acute neurological assessment of the sedated patient.

INTRAVENOUS ANAESTHETIC AGENTS

Propofol

The i.v. anaesthetic agent propofol (2,6-di-isopropylphenol) is frequently used for sedation in the ICU. It is fast acting, very effective and has a rapid offset of action (due to its rapid metabolism to inactive metabolites in the liver). These features make it very suitable for use in patients requiring short-term sedation or for anaesthesia for procedures in the ICU. Although propofol has been shown to reduce time on mechanical ventilation compared with BZA (specifically midazolam) sedation, it has not been shown to reduce time in the ICU.^5,⁶ Caution is required in hypovolaemic patients or those with impaired myocardial function, as severe hypotension may result. Doses for ICU sedation are generally much lower than the 6–12 mg/kg per hour required for anaesthesia. The diluent in which propofol is delivered is lipid-rich and may have to be taken into account as a source of nutrition and indeed cause of hyperlipidaemia, depending on dosage and duration of therapy. Disodium edetate, present in the propofol solution, does not appear to be harmful in patients receiving long-term infusions of propofol.⁷

There has been some recent concern about the so-called ‘propofol infusion syndrome’ where particularly paediatric patients, but also adults, have developed severe heart failure (preceded by metabolic acidaemia, fatty infiltration of the liver and striated muscle damage) after prolonged high-dose infusions of propofol.⁸ Caution should therefore be exercised when using propofol for prolonged periods.

Thiopentone

Thiopentone is reserved for specific indications, such as management of intractable intracranial hypertension (to reduce cerebral metabolism) or for the treatment of status epilepticus. It is not commonly used as a general sedative agent. Its use is limited by its long duration of action and long terminal half-life when used for prolonged infusions.

Ketamine

Ketamine acts by blocking N-methyl-D-aspartic acid (NMDA) receptors. It produces a sedative state known as ‘dissociative anaesthesia’, with the following characteristics:

• mild sedation

• reduced motor activity

The lack of respiratory and cardiovascular depression at lower doses makes this a very safe drug for use in the ICU. Limitations to its use include hallucinations and delirium during the recovery/withdrawal phase. These may be ameliorated by BZA administration. Ketamine may be used specifically for sedation in severe asthmatics (for its bronchodilator effect), in patients following head injury (for its effect at the NMDA receptor) or in patients where analgesia is difficult (e.g. extensive burns).

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