ReviewPropofol: A review of its non-anaesthetic effects
Introduction
Propofol (2, 6-disopropylphenol) is an intravenous short-acting anaesthetic agent that, since its introduction in the late 80s has gained wide acceptance for inducing and maintaining anaesthesia, as well as for sedation. The drug exerts many notable advantages such as minimal side effects, controllable anaesthetic state, quick onset and rapid emergence from general anaesthesia (Glen, 1980, Glen and Hunter, 1984).
Apart from its multiple anaesthetic advantages, propofol exerts a number of non-anaesthetic effects. Ιntravenous anaesthesia with propofol alone seems to be associated with a lower incidence of postoperative nausea and vomiting (Dandoy et al., 1990, Jost et al., 1997, McCollum et al., 1988). Furthermore, it has immunomodulatory activity (Hokey et al., 2005), and may, therefore have an ability to enhance cytotoxic T lymphocyte activity against several types of human tumors. Moreover, propofol acts as a modulator of gamma-aminobutyric acid (GABA A) receptors and experimental studies suggest that propofol's facilitation of these receptors might contribute to analgesia (Dong and Xu, 2002). At doses that do not produce sedation, propofol has anxiolytic effects (Kurt et al., 2003), is a potent antioxidant (Mathy-Hartert et al., 2000) and can lead to memory impairment, especially for memories that are encoded and retrieved by the episodic memory system (Veselis et al., 2008). In addition, in vivo and in vitro studies have revealed propofol's neuro-protective properties (Engelhard et al., 2004, Gelb et al., 2002;). Furthermore, propofol is a modulator of platelet aggregation, (Aoki et al., 1998, Hirakata et al., 1999) NO synthesis (Gonzalez-Correa et al., 2008) and may preserve the endogenous organ protective mechanisms against ischemic or hypoxic injury through its effects on KATP channels. These effects are summarized in Table 1, Table 2, Table 3.
In this review, the experimental and clinical data regarding the commonest non-anaesthetic effects of the intravenous anaesthetic propofol along with the underlying mechanisms are presented. Possible clinical implications are also discussed.
Section snippets
Propofol's antiemetic effects
Numerous studies have demonstrated that propofol possesses direct antiemetic effects. Its use for induction and maintenance of anaesthesia has been associated with a lower incidence of postoperative nausea and vomiting (Dandoy et al., 1990, Jost et al., 1997, McCollum et al., 1988). Borgeat and Stirnemann confirmed that propofol's antiemetic actions really exist (Borgeat and Stirnemann, 1998). Furthermore, they demonstrated that total propofol anaesthesia leads to less postoperative nausea and
Propofol and immunity
Several studies have reported the effects of propofol on cytokine production. In critically ill patients propofol increased serum levels of IL-1β, IL-6 and tumor necrosis factor-α. Additionally, propofol leads to a decrease in IL-2 levels, whereas those of IFN-γ increase as well as in vivo as in vitro (Helmy and Al-Attiyah, 2001, Salo et al., 1997). IFN-γ mediates the differentiation of helper T cells into Th1 lymphocytes, which activate cytotoxic T lymphocyte. Since cytotoxic T lymphocyte is
Propofol and analgesia
Propofol acts as a modulator of GABAA and glycine receptors, which also exist in the spinal cord and have a crucial role in pain transmission (Hales and Lambert, 1991, Millan, 1999, Xu, 1999) and propofol's effect on these receptors might contribute to analgesia (Dong and Xu, 2002). Propofol acts on these receptors, though on a different recognition site from the barbiturates and benzodiazepines, but unlike barbiturates, potentiates glycinergic transmission (Hales and Lambert, 1991) and may
Anxiolytic-like profile of propofol
The effects of propofol on anxiety have not been well investigated. Some experimental studies have demonstrated that propofol produces an anxiolytic effect in animal models (Hara et al., 1993, Matsuo et al., 1997). Kurt et al. reported in a study conducted in mice thatpropofol at 40 and 60 mg/kg can produce anxiolytic-like effects when administrated, both alone or with diazepam, caffeine, l-arginine or m-chlorophenylpiperazine (Kurt et al., 2003). None of the drugs in this study had an effect
Propofol protection during oxidative stress
Propofol's structure contains a phenolic hydroxyl group and thus resembles that of a-tocopherol (vitamin E), a natural antioxidant. As shown by both in vitro and in vivo studies, the antioxidant activity of propofol results partly from this phenolic chemical structure (Ansley et al., 1998). Propofol has been reported to inhibit lipid peroxidation in various experimental models to protect cells against oxidative stress and to increase the antioxidant capacity of plasma in humans (Hans et al.,
Propofol and amnesia
Propofol has been reported to cause dense amnesia, even for intense events (Nordstrom and Sandin, 1996). More vulnerable to propofol's action seem to be memories that are encoded and retrieved by the episodic memory system, whose pivotal component is the hippocampus (Deeprose et al., 2004, Tulving, 2001). Veselis et al. demonstrated that propofol at low doses (0.3, 1.2 or 2.5 μg/mL) had no effect on working memory, which is defined as a short term retention of information no longer available in
Propofol as neuroprotective agent
Propofol has proved to be an efficacious neuroprotective agent in several in vivo and in vitro models of cerebral ischemia (Engelhard et al., 2004, Gelb et al., 2002, Pittman et al., 1997). Although, initial studies with propofol and cerebral ischemia at first yielded contradictory results due to unconventional in vivo models of cerebral ischemia, like those of Kochs et al. (1992) and Tsai et al. (1994), the studies that followed were consistent with the neuroprotective effects of propofol (
Effects of propofol on platelet aggregation
Lysophosphatic acid (LPA) (Nietgen and Durieux, 1998), platelet-activating factor (PAF) (Imaizumi et al., 1995) and thromboxane A2 (TXA2) (Bulger and Maier, 2000) are proinflammatory lipid mediators that are secreted by activated platelets and induce their aggregation. Propofol has been reported to inhibit an LPA receptor response in a Xenopus oocyte model (Rossi et al., 1996). Moreover, it has been reported that propofol has inhibitory effects on platelet aggregation induced by adenosine
Effects of propofol on nitric oxide pathway
Nitric oxide (NO) synthesis requires the participation of nitric oxide synthase (NOS), present in two isoforms: constitutive (cNOS), which is calcium-dependent, and inducible (iNOS), expressed mainly by the presence of inflammatory mediators (Knowles and Moncada, 1994). Propofol has been reported to stimulate NO activities. Moreover, the direct participation of the enzyme NOS, is a fundamental point regarding NO synthesis. It can therefore be suggested that propofol modifies the activity of
Effects of propofol on cardiac sarcolemmal KATP
KATP channels exist in the plasma membranes of various tissues. In cardiac muscle cells, under normal physiologic conditions, KATP channels exist mainly in a closed, inactive form (Noma, 1983). In cardiomyocytes activation of sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channels protects the heart against myocardial ischemia by shortening the duration of the cardiac action (Suzuki et al., 2001). It has been demonstrated that during myocardial ischemia the opening of KATP
Conclusion
In summary propofol is a short-acting intravenous anaesthetic agent that has several advantages, including rapid onset, swift emergence with few side effects and a favorably safety profile. It is obvious that the several nonanaesthetic effects that propofol exerts can substantially change the every day use of propofol and may expand its pharmacological and clinical use. However, more experience and data are needed with nonanaesthetic use of propofol and these characteristics should be further
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