and enhance arousability and the patient ’ s ability to communicate with caregivers . Dexmedetomidine may reduce delirium after long-term sedation as compared with midazolam , 50 and also reduce the overall neurocognitive adverse events of sedation , such as agitation , anxiety , and delirium , compared with propofol . 51
However , safety and efficacy of this drug have not been evaluated in some ICU patient groups , such as patients with acute neurologic disorder ( for example , stroke and head trauma ). 2
Newer alternatives Inhalative sedation in the ICU is starting to spread all over Europe and has been recommended as an alternative in a German consensus guideline . 52 The device used is called AnaConDa ( Anaesthetic Conserving Device ), which makes possible the administration of anaesthetic agents ( isoflurane and sevoflurane ) in any ventilator commonly
53 – 55
found in the ICU . Isoflurane , sevoflurane and desflurane have shown some benefits compared with intravenous sedation . They have a low metabolism and , due to their low solubility , are eliminated quickly and offes shorter and more predictable wake-up times than intravenous agents . 54-58 They can also
53 , 55
prevent the development of bronchospam , have cardioprotective effects 54 and are haemodynamically more stable than intravenous drugs . 55
Some volatile anesthetics abolish cerebral autoregulation at high doses ; it has been reported that at 1.0 MAC sevoflurane , the autoregulation of cerebral blood flow remained intact , but that this was impaired at 2.0 MAC . They also have a direct neuroprotective effect in periods of in vitro 59 and in vivo 60 ischaemia or administered prior to it ( anaesthetic conditioning ). 61 Preconditioning has been described in in vitro 62 and in vivo 63 models of cerebral ischaemia . Sevorane also has a role in post-conditioning ; its application could be of interest once cerebral ischaemia has occurred . Lee et al 64 found that isoflurane post-conditioning reduced brain injury due to ischaemia in rats . However , at 0.5 MAC , adequate neuroprotection is not obtained , which means that the effect of sevoflurane post-conditioning in focal ischaemic lessions is dose-dependent . 65
In a prospective study of sevoflurane sedation in patients with acute stroke or subarachnoid haemorrhage , sufficient sedation levels without clinically relevant ICP increases were achieved in 68 % of patients . 66 However , serious adverse events observed in the remaining 32 % raise considerable safety concerns . Mean arterial pressure ( MAP ) had to be stabilised actively to maintain CPP . Based on these observations , it was concluded that that the alleged neuroprotective potential of sevoflurane do not outweighs the risk of adverse events and sevoflurane sedation should probably not be used in this specific patient population . 66
Volatile sedation has historically been considered unsafe in neurocritical care units around the world . However , as previously mentioned and suggested in several studies , the potential neuroprotective benefit of inhalative sedation has to be more studied .
As well as inhalative sedatives , the use of ketamine has also been debated because of the
concern raised by early studies that it was associated with increased ICP . 67 In studies examining the cerebral haemodynamic effects of ketamine after acute brain injury , ICP was reduced and CPP remained stable or increased , without significant changes in cerebral haemodynamics . 68 A systematic review concluded that ketamine was not associated with an increased risk of ICP elevation , as said previously . 69
Ketamine is a short-acting NMDA receptor antagonist with a rapid onset of action . It does not alter systemic haemodynamics or respiratory drive , therefore it can be used in non-intubated patients . At doses of 1 – 5mg / kg / hour , it can be used as an adjunct to other sedatives to improve their effects and thus limit drug requirements .
Conclusions Sedation and analgesia is frequently used in the management of critically ill patients and is related to a longer hospital stay and more difficult weaning from mechanical ventilation . However , in neurointensive care units , it is also a therapeutic strategy . Therefore studies have been developed to achieve efficient sedation and avoid the adverse effects as much as possible . Midazolam and propofol are the most frequently used first-line sedatives ; however , use of benzodiazepines is less common because of their deleterious effects , such as prolonging mechanical ventilation time and increasing awakening times .
New trends , such as inhalative sedation or ketamine , are beginning to garner more attention , but more studies are required to fully confirm their use .
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