Sedation, analgesia and muscle relaxation in the intensive care unit

Published on 27/02/2015 by admin

Filed under Anesthesiology

Last modified 22/04/2025

Print this page

This article have been viewed 2675 times

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).

Etomidate

Etomidate is no longer used for ICU sedation due to its adrenocortical suppressant (immunosuppressant) action.

MAJOR TRANQUILLIZERS

Butyrophenones (e.g. haloperidol) and phenothiazines (e.g. chlorpromazine) are very useful agents for the sedation of delirious patients in the ICU. They act via a range of receptors including dopaminergic (D₁ and D₂), α-adrenergic, histamine, serotonin and cholinergic receptors. Main actions include:

• reduced motor activity

• apathy and reduced initiative

• sedation and drowsiness

• reduced aggression

Unwanted effects with these drugs are common and include:

• extrapyramidal effects (dystonia and tardive dyskinesia)

• endocrine effects (e.g. lactation)

• anticholinergic effects (e.g. blurred vision, dry mouth, urinary retention, constipation)

• hypotension

• neuroleptic malignant syndrome

The main advantage of major tranquillizers over large doses of minor tranquillizers is that they can be used to gain control in difficult situations (e.g. when delirious patients may be a risk to themselves or their carers) without a major risk of respiratory depression. These agents should not be used for long-term sedation, except where they are used for the specific treatment of psychosis. Typically, haloperidol, diluted to a 1 mg/ml solution, may be given by repeated i.v. injection in doses of 5–20 mg/hour until the delirious patient is approachable. Repeat dosages would then be titrated to allow easy arousal of the patient, with the patient otherwise calm. Haloperidol may also be given by mouth or by i.m. injection.

Olanzapine, a newer ‘atypical’ antipsychotic agent, is also a useful agent for the sedation of delirious patients when given in oral doses of 5–20 mg/day. It has a much lower side-effect profile than the more ‘typical’ antipsychotics, especially with respect to motor side-effects. Olanzapine may also be given as oral/sublingual wafers. This is a particularly useful route of administration in the uncooperative patient.

VOLATILE ANAESTHETIC AGENTS

The widespread use of volatile anaesthetic agents for sedation in the ICU has been limited by:

• the cost of prolonged administration

• the more complex set-up required for the administration of these agents (vaporizer, scavenging apparatus, etc.)

• specific side-effects, e.g. ‘halothane’ hepatitis, accumulation of fluoride ions and consequent renal dysfunction (enflurane and isoflurane) and inactivation of methionine synthase and bone marrow depression (nitrous oxide)

Volatile agents are useful for short periods of anaesthesia during invasive procedures in the ICU. They may be used, with effect, for longer periods for sedation (up to a few days) in acute severe asthma, due to their bronchodilatory action. Short-term administrations of Entonox (50% nitrous oxide in oxygen) are still useful for analgesia and sedation during painful procedures (e.g. removal of intercostal catheters). This may be given by demand valve (controlled by the patient) or be administered by the medical staff.

OPIOIDS

Although opioids are used primarily for their analgesic action in the ICU (see below), they also produce a degree of sedation. They therefore complement the effect of other sedatives used in the ICU, with which they are often given in combination.

DEXMEDETOMIDINE

Dexmedetomidine is a novel highly selective α₂-agonist, which has been shown to provide safe analgesia and sedation in the ICU when given as a single agent by i.v. infusion.⁹

Dosages are: loading dose of 1 μg/kg over 10 min, followed by an infusion of 0.2–0.7 μg/kg per hour.

Infusions longer than 24 hours are currently not recommended. Side-effects may be predicted from the mechanism of action and include hypotension, bradycardia, hypoxaemia and atrial fibrillation. More established α₂-agonists, such as clonidine, may be used to enhance sedation and analgesia when BZA and opioids are used as the mainstay of sedation in the ICU.

ANALGESIA

Pain management is an important priority in the care of critically ill patients.

Many patients present to the ICU with painful conditions or undergo painful procedures during their ICU stay. Pain has a number of adverse consequences:

• it produces anxiety

• it contributes to lack of sleep

• it worsens delirium

• it enhances the stress response – increases circulating catecholamine levels and oxygen consumption

• it results in respiratory embarrassment due to atelectasis and sputum retention

• it leads to immobility and venous and gut stasis

Pain management comprises a number of modalities in addition to analgesics and local and regional anaesthesia/analgesia, such as:

• a caring and supportive medical team that the patient can trust

• warm and comfortable surroundings

• attention to pressure areas (e.g. regular turning)

• the use of warm packs

• the use of simple analgesics as appropriate

• bowel and bladder care

• adequate hydration and amelioration of thirst (e.g. moistening the mouth)

• early tracheostomy where indicated to reduce the discomfort of endotracheal intubation

• splinting and early fixation of fractures.

When drug therapy is required to alleviate pain, the following groups of drugs are commonly used:

• opioid analgesics

• simple analgesics

• non-steroidal anti-inflammatory drugs (NSAIDs)

• novel agents, such as dexmedetomidine (see above) and tramadol

• local anaesthetic agents

• inhaled agents (see volatile anaesthetic agents above)

• ketamine (see above)

• ‘multimodality’ supplemental treatments such as acupuncture, acupressure, massage and transcutaneous electrical nerve stimulation (TENS)

OPIOIDS

Opioids remain the mainstay of analgesia in the ICU. This group of drugs encompasses:

• morphine and its analogues (e.g. morphine, diamorphine, codeine)

• semisynthetic and synthetic agents

• phenylpiperidine derivatives (e.g. pethidine, fentanyl)

• methadone derivatives (e.g. methadone, dextropropoxyphene)

• benzomorphan derivatives (e.g. pentazocine)

• thebaine derivatives (e.g. buprenorphine)

The effects of opioids are mediated via the three main opioid receptor subtypes μ, κ and σ. These G-protein coupled receptors inhibit adenyl cyclase and effects include:

• analgesia (supraspinal, spinal and peripheral)

• pupillary constriction

• respiratory depression and cough suppression

• euphoria or dysphoria

• reduced gastrointestinal motility

• physical dependence

Opioids are titrated to effect by intermittent injection (usually i.v. in the ICU) or by continuous infusion, which may be nurse controlled (nurse-controlled analgesia, NCA) or controlled by the patient (patient-controlled analgesia, PCA). A suitable regimen is a 1 mg/ml dilution of morphine given by continuous i.v. infusion, titrated to patient comfort. This is often combined with a BZA (e.g. midazolam) to produce a ‘sedative/analgesic’ infusion for use in very ill patients on mechanical ventilation (see sedation above). Opioids are also administered via the subarachnoid, extradural, transdermal and intranasal routes.

The effect of analgesia in the clinical setting is judged by:

• patient response, if they are conscious, either verbally by describing the level of pain subjectively or by using a visual analogue score (Figure 81.1)³ or other assessment, such as behavioural pain scales¹⁰

• physiological markers of distress, e.g. tachycardia, hypertension, diaphoresis, restlessness

Figure 81.1 Visual analogue score for the assessment of pain.³

These indicators should be assessed in the clinical context, i.e. is the pathophysiological process likely to be responsible for some, or considerable pain? Analgesia should be administered for a specific indication and to desired effect. Many factors lead to a wide variation in the experience of pain including:

• personality traits

• the previous experience of pain

• interpretation of events/disorientation/deperonalization

• degree of tissue damage

• chronic disease and debility

In the critically ill, the use of opioids may be complicated by:

• wide interindividual responses to similar dosages, mandating titration of the analgesic, especially in debilitated and elderly patients

• severe hypotension following rapid administration, particularly in hypovolaemic patients. Fentanyl and sufentanil may offer advantages over morphine in terms of ‘cardiostability’

• prolonged duration of action, due to accumulation of parent compound and metabolites (e.g. morphine and its major metabolites morphine-3-glucuronide and morphine-6-glucuronide) in the elderly and in patients with renal and hepatic dysfunction. Use of drugs with shorter half-lives (e.g. alfentanil) or which are less dependent on hepatic and renal pathways for metabolism and excretion (e.g. remifentanil) can reduce this problem

• constipation, requiring careful attention to detail and the judicious use of prokinetic agents (e.g. metoclopramide, erythromycin) to overcome gastric stasis and enable enteral feeding, or prurients to aid evacuation

• the development of tolerance requiring increasing doses to achieve the same effect

Early recognition of these symptoms of withdrawal is not always simple in the ICU patient and may be mistaken for sepsis or delirium. Treatment is by re-institution of and then slow withdrawal of the opioid, especially after prolonged periods of administration. Alternatively, symptoms may be controlled with a combination of long-acting opioid (e.g. methadone), BZA and α₂-agonists (e.g. clonidine).

A knowledge of drug-related (as opposed to class-related) side-effects is important when using opioids other than morphine, e.g. the interaction between pethidine and the older monoamine oxidase inhibitors, the potential for seizures with high dose or prolonged use of pethidine, chest wall rigidity occasionally seen with high doses of fentanyl.

The specific opioid antagonist naloxone has little role to play in the ICU, except for the treatment of severe hypotension, unwanted sedation or respiratory depression following opioid usage. Rapid reversal of opioid effect for the purpose of neurological assessment may be another valid use of naloxone.

SIMPLE ANALGESICS

Paracetamol and other simple analgesics (e.g. salicylates) are particularly effective for:

• bone and joint pain

• soft tissue pain

• perioperative pain

• inflammatory conditions

• as part of multimodal analgesia, to reduce opioid requirements

These drugs are given by mouth, via a nasogastric tube, per rectum or i.v. to supplement analgesia in the critically ill (e.g. paracetamol 1–2 g 4–6-hourly). Use is limited by the risk of hepatic dysfunction if used in high dose or for prolonged periods.

NSAIDs

The commonly used NSAIDs are carboxylic acids (e.g. indometacin, ibuprofen, mefenamic acid) or enolic acids (e.g. piroxicam). NSAIDs are useful for supplemental/multimodal analgesia in the ICU for the conditions listed for simple analgesics above. They are given by mouth, via a nasogastric tube, per rectum or by i.m. injection (e.g. indometacin 100 mg twice daily PR or ketorolac 10–15 mg 4–6-hourly i.m.) for pain and pyrexia. Side-effects include:

• renal dysfunction

• gastrointestinal haemorrhage

• increased bleeding tendency due to platelet inhibition

The newer cyclooxygenase 2 (COX-2) specific inhibitors, such as valdecoxib and its injectable precursor parecoxib, have a much lower side-effect profile than traditional NSAIDs. These drugs should be used only for short periods, due to recent evidence regarding increased cardiovascular morbidity associated with long-term use of the COX-2 inhibitors.¹¹

TRAMADOL

Tramadol is a more recent addition to the analgesic range. It acts via the μ receptor, as well as by inhibiting the uptake of serotonin and noradrenaline (norepinephrine), with presynaptic stimulation of serotonin release, thereby enhancing the effects of the descending analgesia system. It is useful for moderate to severe pain in the postoperative patient in doses of 50–100 mg i.v., oral or i.m. 4–6-hourly to a maximum of 600 mg/day.

LOCAL ANAESTHETICS – REGIONAL ANAESTHESIA/ANALGESIA

The use of local anaesthetic techniques in the critically ill patient is limited by:

• pain often emanating from multiple sources, and therefore not amenable to a single regional technique

• the requirement for ‘mandatory’ sedation/analgesia in order for the patient to tolerate endotracheal intubation, making a regional technique for another source of pain (e.g. laparotomy wound) superfluous

• the need to treat pain over a prolonged period, mandating either repetition of the regional block (e.g. intercostal nerve blocks for pain from an upper abdominal incision, or femoral nerve blocks for a fractured femur) or the placement of an indwelling catheter (e.g. epidural catheter). Indwelling catheters also have a defined safe duration of insertion (usually 3–4 days) before they need to be removed and replaced

• coagulopathy frequently seen in this group of patients, making procedures such as epidural injection less safe

• comorbidities (e.g. severe ischaemic heart disease) in the critically ill patient

When a regional technique is considered viable (e.g. thoracic epidural for the treatment of pain due to fractured ribs), then the following need to be considered:

• the procedure should be carried out by adequately trained personnel (usually with an anaesthesia background)

• regional techniques may be very time-consuming, requiring additional staff to properly position the patient and assist the proceduralist

• regional techniques may carry serious complication risks (e.g. subarachnoid injection of local anaesthetic or epidural haematoma during placement of epidural catheters, with serious haemodynamic, neurological and respiratory consequences)

• good preparation is paramount:

• informed consent from patient or legal surrogate

• recent normal coagulation profile, or correction of abnormal profile

• the knowledge and ability to deal with complications (e.g. sudden hypotension)

• experience with the drugs being used (typically a mixture of local anaesthetic, such as ropivacaine 0.2%, and an opioid, such as fentanyl 2 μg/ml, are used for epidural infusion)

• adequate training of nursing staff to monitor the level of block, haemodynamic parameters and for possible complications

Within the context above, the following blocks may be useful in individual patients:

• femoral nerve block for lower limb injuries (10 ml of 7.5 mg/ml ropivacaine injected intermittently 8–12-hourly into the region of the femoral nerve immediately inferior to the inguinal ligament)

• intercostal nerve blocks for thoracic and upper abdominal injuries or wounds (2–3 ml of 7.5 mg/ml ropivacaine injected into the region of appropriate intercostal nerves – usually at three or four sites unilaterally or bilaterally)

• brachial plexus or i.v. regional anaesthesia for isolated upper limb injuries or procedures (e.g. fracture manipulation)

• epidural analgesia for thoracic and abdominal pain

• intrapleural analgesia/anaesthesia, applied either via a catheter placed for this purpose or via intercostal drains previously placed for treatment of pneumothorax

MUSCLE RELAXANTS

The routine use of muscle relaxants for prolonged periods is a rare occurrence in the ICU since the advent of mechanical ventilators that provide assisted modes of ventilation (as opposed to mandatory modes used previously). Spontaneous assisted ventilation for almost all mechanically ventilated patients is now encouraged. Current indications for the use of muscle relaxants in the ICU include:

• to complement general anaesthesia for endotracheal intubation and initiation of mechanical ventilation or for short surgical procedures (e.g. tracheostomy)

• to facilitate the safe transport of patients and the acquisition of adequate radiographic images (e.g. CT or MRI)

• to facilitate mandatory mechanical ventilation when adequate sedation/analgesia alone is not adequate to achieve control, for example:

• to increase chest wall compliance (e.g. in the severe asthmatic or to facilitate venous drainage in the patient with severe intracranial hypertension)

• to facilitate precise control of respiratory parameters, such as airway pressure or PaCO₂ (e.g. permissive hypercapnia in patients with acute respiratory distress syndrome or normocapnia in patients with impaired cerebral autoregulation)

• to reduce VO₂ in the severely hypoxaemic patient

• specific indications, such as treatment of muscle spasm in tetanus

Before muscle relaxants are used, patients should already be (or about to be commenced) on mechanical ventilation, there should be the expertise and equipment available to deal with ‘difficult intubation’ or accidental extubation, and patients should be sedated/anaesthetised to prevent the awareness of being paralysed while inadequately sedated. Muscle relaxants may be given by intermittent i.v. injection or by continuous i.v. infusion.

CHOICE OF MUSCLE RELAXANT

Depolarising muscle relaxants are to be used with caution in the ICU patient who has:

• multiple injuries

• renal failure

• neurological problems (e.g. paraplegia)

• been immobilised for a prolonged period of time

The risk of severe hyperkalaemia following administration of suxamethonium in these settings is high. Rocuronium, a rapid-onset, non-depolarising muscle relaxant, may be a suitable alternative.

Non-depolarising agents are the most commonly used relaxants in the ICU. Their use may be complicated by:

• Accumulation of the parent compound or active metabolites in patients with hepatic or renal insufficiency. Atracurium and cisatracurium are useful agents in these patients due to their inactivation pathways being independent of the kidney and the liver. Accumulation of the epileptogenic metabolite laudanosine may be a problem with atracurium.

• Histamine release following usually rapid injection of certain of these agents (e.g. atracurium). Vecuronium has been shown to be very ‘cardiostable’.

• Protective reflexes (e.g. cough, gag, blink) are abolished and the patient is not able to move and posture him/herself. This requires increased vigilance and attention from the attendants.

• Neurological assessment of the paralysed patient is not possible and requires strict attention to detail to ensure the patient is adequately sedated while paralysed.

• Prolonged duration of action may result from:

• patient factors, such as electrolyte disturbances (e.g. hypokalaemia, hypophosphataemia)

• drug factors, such as myopathy associated with the use of steroidal relaxants (e.g. pancuronium, vecuronium), especially when used in conjunction with corticosteroids or aminoglycoside antibiotics.

When muscle relaxants are to be used, they should be used for a clearly defined indication, for as short a time as possible. In addition, the appropriate drug should be used and its use should be monitored regularly (e.g. train of four, post-tetanic count or double burst stimulation). Alternatively, muscle relaxants may be withheld at least once a day, until the return of muscle activity. This drug-free period may be combined with a sedation-free period every day in stable patients to allow adequate neurological assessment.

1 Rhoney DH, Parker DJ. Use of sedative and analgesic agents in neurotrauma patients: effects on cerebral physiology. Neurol Res. 2001;23:237-259.

2 MacLaren R, Plamondon JM, Ramsay KB, et al. A prospective evaluation of empiric versus protocol-based sedation and analgesia. Pharmacotherapy. 2000;20:662-672.

3 Wiener-Kronish JP. Problems with sedation and analgesia in the ICU. Pulm Pers. 2001;18:1-3.

4 Kress JP, Pohlman AS, O’Connor MF, et al. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342:1471-1477.

5 Hall RI, Sandham D, Cardinal P, et al. Propofol vs midazolam for ICU sedation: a Canadian multicenter randomized trial. Chest. 2001;119:1151-1159.

6 Walder B, Elia N, Henzi I, et al. A lack of evidence of superiority of propofol versus midazolam for sedation in mechanically ventilated critically ill patients: a qualitative and quantitative systemic review. Anesth Analg. 2001;92:975-983.

7 Abraham E, Papadakos PJ, Tharratt RS, et al. Effects of propofol containing EDTA on mineral metabolism in medical patients with pulmonary dysfunction. Intensive Care Med. 2000;26(Suppl 4):S422-S432.

8 Bray RJ. The propofol infusion syndrome in infants and children: can we predict the risk? Curr Opin Anaesthesiol. 2002;15:339-342.

9 Nasraway SA. Use of sedative medications in the intensive care unit. Semin Respir Crit Care Med. 2001;22:165-174.

10 Aissaoui Y, Zeggwahg AA, Zekraoui A, et al. Validation of a behavioural pain scale in critically ill, sedated and mechanically ventilated patients. Anesth Analg. 2005;101:1470-1476.

11 Lee YH, Ji JD, Song GG. Adjusted indirect comparison of celecoxib versus rofecoxib on cardiovascular risk. Rheumatol Int. 2007;27:477-482.

Related

Ohs Intensive Care Manual 6e