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of high-quality illustrations as part of review articles, the British Journal of Anaesthesia will be encouraging authors 1 Laurence D. What is pharmacology? A discussion. Trends Pharmacol of all future review articles to include figures suitable for colour reproduction wherever appropriate.
2 Power I. Fentanyl HCl iontophoretic transdermal system (ITS): clinical application of iontophoretic technology in the management of acute postoperative pain. Br J Anaesth 2007; 98: 4 – 11 3 Hendrickx JFA, Eger EI, II, Sonner JM, Shafer SL. Is synergy the rule? A review of anesthetic interactions producing hypnosis and immobility. Anesth Analg 2008; 107: 494 – 506 4 Preckel B, Weber NC, Sanders RD, Maze M, Schlack W. Molecular mechanisms transducing the anesthetic, analgesic, and organ- protective actions of xenon. Anesthesiology 2006; 105: 187 – 97 5 Colvin LA, Lambert DG. Pain medicine: advances in basic sciences and clinical practice. Br J Anaesth 2008; 101: 1 – 4 6 Joshi GP. Intraoperative fluid restriction improves outcome after major elective gastrointestinal surgery. Anesth Analg 2005; 101: 601–5 7 Otsuki DA, Fantoni DT, Margarido CB, et al. Hydroxyethyl starch is superior to lactated Ringer as a replacement fluid in a pig model of acute normovolaemic haemodilution. Br J Anaesth 2007; 98: 29 – 37 British Journal of Anaesthesia 103 (1): 2 – 5 (2009) Advances in patient comfort: awake, delirious, or restrained In this editorial, three aspects of comfort of intensive care it because of a surgical wound, traumatic injury, pleuritic patients will be explored: avoiding unnecessary coma; pain, or immobility. If they are receiving mechanical ven- delirium; and physical vs pharmacological restraint.
tilation, then tracheal tube tolerance along with reversibleand titratable respiratory depression may also be needed.
These are best provided by opioids. Notably, hypnosis is not a necessary component of what most patients need or Most intensive care units (ICUs) in the UK have a signifi- want. It should be reserved for patients who cannot be cant input from anaesthetists. Anaesthetists are used to managed with opioids (about one-third of patients only)4 rendering patients unconscious, primarily so that they do not suffer during surgery. Critically ill patients are also This approach reduces length of stay in the ICU and the often kept unconscious and nothing is seen as unusual or period of mechanical ventilation. It also saves money wrong with this. There is increasing evidence that when compared with conventional (hypnosis-based) seda- unnecessary sedation may increase patient morbidity and tion and analgesia.2 Remifentanil, for example, has been shown to reduce the need for hypnotics by two-thirds and The quantity and quality of staff available influence the is increasingly used for the critically ill, usually without amount of sedation given. Natural light and a clock orien- hypnotic drugs.4 There is substantial evidence that remi- tate patients while reducing noise from alarms, etc., fentanil reduces duration of mechanical ventilation and encourages sleep. Communication problems can cause length of stay in the ICU.4 – 6 Although its acquisition cost frustration and agitation, which will be exacerbated by is high, the savings mean that it can reduce costs by poor hearing, eyesight, or both. The adverse effects of E1000 per patient compared with other regimens.2 Not sedatives are widely known,3 yet they are often given in an only is there a cost saving, but there are other benefits, such as better interaction with family and carers, ability to One of the best ways to avoid many of the problems move (reducing the nursing workload), and cooperating patients experience with sedation is to think about the with the physiotherapist. Finally, it allows patients who needs of the patient. Almost all patients need analgesia, be delusions to be recognized. This is especially important when these occur as patients are going off to sleep (hypno- Antipsychotics have been the traditional mainstay in the gogic), since they may try to avoid sleeping so as not to acutely confused patient, in response to the theory that suffer from these sometimes terrifying experiences. This delirium may be caused by a dopaminergic/muscarinic may help reduce psychological sequelae after ICU.
imbalance in the brain, although evidence for this Dreams occurring on waking (hypnopompic) are usually approach is limited. Haloperidol is the most widely used drug in the treatment of delirium and is recommended inmost guidelines,11 12 despite the lack of any randomizedcontrolled trials. It has been studied in the prevention of delirium in postoperative patients and reduced the severity This is an acute disorder of attention and global cognitive and duration of delirium episodes but did not reduce their function, characterized by acute onset and fluctuating symptoms, which is associated with increased morbidity.
Haloperidol inhibits symptoms such as hallucinations, It is not a disease but a syndrome and has multiple causes.
delusions, and unstructured thought patterns but also In the event of failure to respond to preventative and sup- diminishes the patient’s interest in their environment portive measures, pharmacological treatment may be leading to a flattened affect. High doses may be associated needed. Early identification and prompt treatment may with clinically significant prolongation of the QT interval reduce the severity and duration of delirium.
of the ECG and neuroleptic malignant syndrome.
Droperidol is more potent than haloperidol but is associ- ated with frightening dreams and increased hypotension.
Chlorpromazine is also effective at treating delirium but is The classical form of hyperactive delirium, characterized associated with anticholinergic side-effects that have been by agitation and restlessness, is quite rare in critically ill implicated in the development of delirium.
patients (incidence 1.6%). The common forms are hypoac- Recently, there has been increasing interest in the use of tive delirium, characterized by withdrawal and apathy the atypical antipsychotics, including olanzipine, risperi- (incidence 43.5%) and mixed (incidence 54.9%).7 Until done, and quetiapine. A recent meta-analysis comparing recently, a lack of recognition of these hypoactive states olanzipine and risperidone with low-dose haloperidol has and the fluctuating course of delirium led to significant shown that the three drugs have similar efficacy, but that high-dose haloperidol was associated with increased extra- The severity of illness and a lack of verbal communi- cation in these patients have led to the development of Benzodiazepines are only recommended in the treatment validated ICU-specific delirium screening tools. The most of delirium associated with alcohol withdrawal syndromes.
commonly used are CAM-ICU8 and Intensive Care In patients with AIDS, lorazepam was ineffective at treat- Delirium Screening Checklist (ICDSC).9 CAM-ICU is ing delirium and led to a high incidence of side-effects quick and simple to perform and has been shown to have compared with haloperidol.14 A short-acting benzo- excellent sensitivity and specificity. As under-recognition diazepine, such as midazolam, may be given in conjunc- of delirium is associated with a poorer outcome, routine tion with haloperidol to control an acutely agitated patient assessment by one of these methods at least once in every who is at risk to themselves or others.
Benzodiazepines may increase the duration and incidence When patients become agitated or confused, they risk of delirium in ICU patients, whereas using alpha-2 adre- harm to themselves and others. In this situation, there is a nergic agonists such as dexmedetomidine may reduce it.
place for restraint, either physical, chemical, or both to Dexmedetomidine is currently not licensed for use in the maintain a safe environment for patients and their carers.
UK, but has sedative, analgesic, anxiolytic, and sympatho- Recent American guidelines15 advocate the greater use of lytic actions without depressing respiratory function. Its physical over chemical restraint. At the same time, UK side-effects include bradycardia and hypotension. Using guidelines16 proposing the opposite emphasis have been dexmedetomidine rather than lorazepam for sedation is associated with more delirium- and coma-free days, moreventilator-free days, and a reduced risk of death at28 days.10 When compared with midazolam, there was a shorter time to tracheal extubation and a shorter ICU stay In the UK, agitation is usually controlled with drugs with dexmedetomidine. These studies suggest that the (chemical restraint). While this is generally regarded as future of delirium therapy may lie in its prevention.
kind, these drugs carry their own risks. In other countries, Table 1 The risks and benefits of physical vs chemical restraint Stops immediate physical harm to patients unrecognized comaToxic side-effects of drugs, especially cardiovascular and CNSAccidental self-extubation drugs are used less and physical restraint as a way of restricting a patient’s freedom of movement is common.
The relative risks of both are poorly understood and are Family objection is often quoted as a reason for not using physical restraints, but there is no evidence for this.
There are two main legal issues with both physical andchemical restraint in the UK. The first involves the law ofassault, the threat of violence, and battery, the actual and direct use of unlawful physical force on another person, 1 Kress JP, Pohlman AS, O’Connor MF, Hal JB. Daily interruption of even if they are not actually harmed. The second legal sedative infusions in critically ill patients undergoing mechanical issue is the risk of negligence. For example, if a patient is ventilation. N Engl J Med 2000; 342: 1471 – 7 sedated because of agitation and as a result, their ICU 2 Al M, Hakkaart L, Tan S, Mulder P, Bakker J. Remifentanil vs admission is prolonged, is this negligent? conventional sedation in The Netherlands: a pharmacoeconomic The ethical issues surrounding restraint in the confused model analysis. Crit Care 2007; 11(Suppl 2): 427 3 Park GR. Molecular mechanisms of drug metabolism in the criti- patient centre around the risk – benefit balance, benefi- cally ill. Br J Anaesth 1996; 77: 32 – 49 cence, and non-maleficience and around patient autonomy.
4 Park G, Lane M, Rogers S, Bassett P. A comparison of hypnotic The use of restraint must respect a patient’s autonomy and and analgesic based sedation in a general intensive care unit. Br J autonomous patients must not be restrained without consent. Using the CAMICU score,8 17 as part of estab- 5 Mu¨llejans B, Lo´pez A, Cross MH, Bonome C, Morrison L, lishing a need for restraint, helps to clarify this issue.
Kirkham AJT. Remifentanil versus fentanyl for analgesia based Chemical and physical restraints are legally and ethi- sedation to provide patient comfort in the intensive care unit: arandomized, double-blind controlled trial. Crit Care 2004; 8: cally the same but are regarded very differently. Chemical rather than physical restraint is preferred in the UK 6 Mu¨llejans B, Matthey T, Scholpp J, Schill M. Sedation in the inten- because sedation is thought more caring, a perception sive care unit with remifentanil/propofol versus midazolam/fenta- which may be inaccurate. Sedative agents are administered nyl: a randomised, open-label, pharmacoeconomic trial. Crit Care without specific training in their use while training is required to use physical restraints appropriately. Perhaps 7 Peterson JF, Pun BT, Dittus RS, et al. Delirium and its motoric sub- training in techniques of restraint for all ICU staff would types: a study of 614 critically ill patients. J Am Geriatr Soc 2006;54: 479 – 84 8 Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of CAM-ICU. J Am MedAssoc 2001; 286: 2703 – 10 9 Bergeron N, Dubois MJ, Dumont M, et al. Intensive Care Delirium Screening Checklist: evaluation of new screening tool. Intensive G.R.P. has given lectures for GlakoSmithKline and received research funding from them. The other authors 10 Riker R, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs have no conflicts of interest to declare.
midazolam for sedation of critically ill patients: a randomisedcontrolled trial. J Am Med Assoc 2009; 301: 489 – 99 11 UKCPA/ICS Guidelines for detection, prevention and treat- ment of delirium in critically ill patients. Available from http://www.ukcpa.org/ukcpadocuments/6.pdf (accessed April 17, 12 Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines 15 Maccioli GA, Dorman T, Brown BR, et al. Clinical practice guide- for the sustained use of sedatives and analgesics in the critically lines for the maintenance of patient physical safety in the inten- ill adult. Crit Care Med 2002; 30: 119 – 41 sive care unit: use of restraining therapies—American College of 13 Kalisvaart KJ, de Jonghe JFM, Bogaards MJ, et al. Haloperidol pro- Critical Care Medicine Task Force 2001 – 2002. Crit Care Med phylaxis for elderly hip-surgery patients at risk for delirium: a randomised placebo-controlled study. J Am Geriatr Soc 2005; 53: 16 Bray K, Hill K, Robson W, et al. British Association of Critical Care Nurses position statement on the use of restraint in adult 14 Breitbart W, Marotta R, Platt MM, et al. A double-blind trial of critical care units. Nurs Crit Care 2004; 9: 199 – 212 haloperidol, chlorpromazine and lorazepam in the treatment of 17 Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically delirium in hospitalised AIDS patients. Am J Psychiatry 1996; 153: ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001; 29: 1370–9 British Journal of Anaesthesia 103 (1): 5 – 6 (2009) Neurokinin-1 antagonists: a step change in prevention of postoperative nausea and vomiting? The ability to reliably treat and prevent postoperative factors. Four of the most important risk factors are: female nausea and vomiting (PONV) still remains elusive, despite gender, non-smoking, previous history or motion sickness, significant advances in our understanding of the physi- and the use of perioperative opioids.6 It has been estimated ology of emesis and availability of several new antie- that the risks of PONV after inhalation anaesthesia is 10%, metics. This is unfortunate as patients are really concerned 20%, 40%, 60%, or 80% in the presence of none, one, about, and often fear, nausea and vomiting in the peri- two, three, or four of these factors, respectively.6 The inci- operative period. However, although of concern, it is not dence may be less with total i.v. anaesthesia, but there is considered by many anaesthetists as one of the most no doubt that PONV is still a common and troublesome important things to avoid during anaesthesia. For example, a group from San Diego asked a panel of expert anaesthe- tists what clinical anaesthesia outcomes are both common summary of the relative efficacy of antiemetics used for and important to avoid.1 The list in order of importance PONV7 (Table 1). These data show relatively disappoint- was reported as: death, recall with pain, nerve injury, ing efficacy compared with placebo (especially with recall without pain, damage to teeth, corneal abrasion, respect to nausea) and the need for better therapy. The vomiting, post-dural puncture headache, pain, and nausea.
1990s saw the introduction of the 5-HT3 antagonists Patients’ perception of problems to avoid during anaesthe- with claims by some that they heralded the end of sia is very different. They expect to survive, most regard PONV. Sadly, this was not the case; data in Table 1 being asleep and unaware as par for the course, and most show how they compare with others. These disappointing would not expect to awake with damaged nerves, eyes, or results gave impetus to the developing concept at that teeth. Indeed, the same team in San Diego asked patients time of multiple therapy for PONV which was proving what outcomes they thought were important to avoid to be more effective than monotherapy.8 This approach during anaesthesia.2 Their response in order of importance has now become standard practice in many clinical situ- was: vomiting, gagging on the endotracheal tube, nausea, ations and has been adopted in national and local guide- recall without pain, residual weakness, shivering, sore lines for the prevention of PONV, especially in high-risk throat, and somnolence. Another measure of how much PONV is an issue for patients is to ask them how much Mortality from anaesthesia in developed health-care ser- they would pay to be free from emesis after surgery. In vices, although devastating, is very rare; service improve- 2001, a survey of patients in the USA revealed that they ments are focused on quality and PONV is a major issue were willing to pay $55 – 100.3 Quite a sum when you in this regard. In addition, the complications associated with PONV are well known, for example, aspiration of The incidence of PONV is still generally regarded as stomach contents, disruption of surgical sutures, dehy- 30%,4 5 but clearly depends on patient and surgical dration, and electrolyte disturbance. Clearly, this problem

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