Kelly, Daniel F.
Section Editor(s): De Deyne, C.; De Jongh, R.; Heylen, R.; Van Aken, H.
Broadly defined, a sedative is 'an agent that allays excitement' . Severely head-injured patients are often treated with sedatives for agitation, fluctuating ventilatory capacity and acute increases in intracranial pressure (ICP). The most commonly used sedatives in the management of comatose head-injury patients include benzodiazepines, opioid narcotics and propofol. Sedative regimens, however, remain nonstandardized and it is unclear whether sedation per se has a significant impact on outcome. In the evidence-based 'Guidelines for the management of severe head injury' , no standards or guidelines could be supported regarding the use of these agents. Only the following option was offered: 'Sedation and neuromuscular blockade can be useful in optimizing transport of the head-injured patient. However, both treatments interfere with the neurological examination. In the absence of outcome-based studies, the choice of sedative is left to the physician. Neuromuscular blockade should be employed when sedation alone proves inadequate, and short-acting agents should be used when possible.' Unfortunately, since 1996, the uncertainty regarding choice of sedative for head-injured patients persists.
The most commonly used sedative regimens typically include the following: (1) an opiate narcotic such as morphine or fentanyl, with or without a neuromuscular blocking agent [3,4]; (2) an opiate narcotic with a benzodiazepine such as midazolam ; or (3) a combination of all three, i.e. opiate, benzodiazepine and neuromuscular blocking agent . Alternatively, a propofol regimen with narcotic analgesics and neuromuscular blocking agents, as needed, is also commonly employed [6,7]. A major problem in attempting to determine the relative effectiveness of these agents is defining the goals of therapy. The endpoints typically cited include effective sedation and analgesia, controlled ventilation and ICP control. Additional considerations might include whether an agent has neuroprotective effects and its cost.
The opiate narcotics while providing excellent analgesia, are commonly used for sedation. At higher doses, they are heavily sedating and depress respiratory drive. One problem with using opiates in head-injured patients is their lack of effect on ICP. Neither morphine, fentanyl nor sufentanil reliably decrease ICP in severe head-injury patients [8,9]. In one report, both fentanyl and sufentanil increased ICP in such patients . Midazolam, the short-acting benzodiazepine, is a very effective sedative with anticonvulsant properties, but lacks analgesic effects . It also does not reliably decrease ICP in severe head-injury patients and in bolus administration will significantly decrease cerebral perfusion pressure .
Propofol, the short-acting sedative, nonanalgesic agent, has been shown in several studies to be safe and possibly more effective than a narcotic-based or benzodiazepine-based regimen in head-injured patients [3,7,13]. Propofol is potentially advantageous over midazolam because of its neuroprotective and metabolic suppressive effects seen at higher doses [14-18], its effect on ICP [3,7], and because high-dose propofol does not impair CO2 reactivity or cerebral pressure autoregulation [19,20]. The major problem with prolonged high-dose propofol appears to be hypertriglyceridaemia from the lipid vehicle, which has been associated with adverse outcomes, particularly in the paediatric population, although this remains controversial . A 2% formulation that reduces the lipid load by 50% will hopefully eliminate or greatly reduce lipid-related adverse events seen with the 1% formulation. This 2% formulation is currently available in Europe but not in the USA.
Regarding haemodynamics, the opioids, benzodiazepines and propofol, when given rapidly or in bolus form, can all induce a precipitous reduction in blood pressure [8,12,22,23]. This effect can be minimized if patients have a normal intravascular volume prior to initiating therapy and if the dose is gradually increased. Finally, regarding the issue of cost, propofol is clearly more expensive than the opiate narcotics and the benzodiazepines on a per unit basis. However, most intubated head-injured patients are not adequately sedated with an opiate or a benzodiazepine alone. In contrast, a propofol-based sedation regimen can reduce the need for concomitant opiates, benzodiazepines and muscle relaxants . Additionally, patients on propofol tend to have a more rapid emergence from sedation compared with those on benzodiazepines, which may in turn shorten mechanical ventilation time, time in the ICU, and overall hospital costs [11,24,25]. In summary, a variety of sedative regimens using opiates, benzodiazepines and/or propofol have all been shown to be relatively effective in the management of severe head-injured patients. Each of these regimens also has drawbacks. Further carefully conducted studies are required to clearly demonstrate whether a given sedative regimen actually improves neurological outcome.
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25 Sanchez-Izquierdo-Riera JA, Caballero-Cubedo RE, Perez-Vela JL et al. Propofol versus midazolam: safety and efficacy for sedating the severe trauma patient. Anesth Analg, 1998; 86: 1219-1224.
The publication of this supplement has been supported by an educational grant from GlaxoWellcome
Session 5: Severe Head Injury