Subanaesthetic Doses Of Propofol Research Articles

Propofol Alleviates Intractable Migraine Headache: A Case Report

Several medications have been proposed as the first line drugs in the treatment of migraine attack. However, the low efficacy, potential complications of medications and the intolerance of some patients for oral route due to nausea and vomiting establish a difficult situation in some migraine patients. This report describes a dramatic pain relief with 60 mg of intravenous propofol in a patient with migraine attack refractory to treatment with metoclopramide, promethazine, dexamethasone and meperidine. Pain relief in this patient besides earlier case reports suggests that subanesthetic doses of propofol may be an alternative to other treatment modalities for acute migraine.

The Rivers of Lethe and Mnemosyne Converge

The Rivers of Lethe and Mnemosyne Converge

Modulation of exteroceptive suppression periods in human jaw‐closing muscles by subanaesthetic dose of propofol

Exteroceptive suppression (ES) periods in human jaw-closing muscles can be conditioned by a wide range of somatosensory stimuli and cognitive states. The aim of this study was to examine the effects of subanaesthetic doses of midazolam, ketamine and propofol on the short latency (ES1) and long latency (ES2) reflex in the jaw-closing muscles. First, we tried to evaluate the various methodological criteria for ES recording. We then examined the effect of subanaesthetic doses of midazolam (0·035 mg kg(-1)), ketamine (0·30 mg kg(-1)) and propofol (0·35 mg kg(-1)) on these reflexes of recording left masseter and temporalis muscle. ES duration did not differ greatly in the present study, recorded with the correct adjustment of stimulating and recording conditions. None of the subanaesthetic doses of the agents influenced ES1, and no significant effects on ES2 were observed with midazolam and ketamine. However, significant inhibitory change was observed in ES2 with propofol. ES2 is thought to be mediated by afferents, which descend in the spinal trigeminal tract and connect with a polysynaptic chain of excitatory interneurones located in the lateral reticular formation. Our observations indicate that propofol is uniquely effective not only through involvement of the gamma-aminobutyric acid type A receptor, but also through a range of other effects.

Propofol restores the function of "hyperekplexic" mutant glycine receptors in Xenopus oocytes and mice.

Human hereditary hyperekplexia ("startle disease") is a neurological disorder characterized by exaggerated, convulsive movements in response to unexpected stimuli. Molecular genetic studies have shown that this disease is often caused by amino acid substitutions at arginine 271 to glutamine or leucine of the alpha1 subunit of the inhibitory glycine receptor (GlyR). When exogenously expressed in Xenopus oocytes, agonist responses of mutant alpha1(R271Q) and alpha1(R271L) GlyRs show higher EC50 values and lower maximal inducible responses (relative efficacies) compared with oocytes expressing wild-type alpha1 GlyR subunits. Here, we report that the maximal glycine-induced currents (I(max)) of mutant alpha1(R271Q) and alpha1(R271L) GlyRs were dramatically potentiated in the presence of the anesthetic propofol (PRO), whereas the I(max) of wild-type alpha(1) receptors was not affected. Quantitative analysis of the agonist responses of the isofunctionally substituted alpha1(R271K) mutant GlyR revealed that saturating concentrations of PRO decreased the EC50 values of both glycine and the partial agonist beta-alanine by >10-fold, with relative efficacies increasing by 4- and 16-fold, respectively. Transgenic (tg) mice carrying the alpha1(R271Q) mutation (tg271Q-300) have both spontaneous and induced tremor episodes that closely resemble the movements of startled hyperekplexic patients. After treatment with subanesthetic doses of PRO, the tg271Q-300 mutant mice showed temporary reflexive and locomotor improvements that made them indistinguishable from wild-type mice. Together, these results demonstrate that the functional and behavioral effects of hyperekplexia mutations can be effectively reversed by drugs that potentiate GlyR responses.

Intravenous propofol: unique effectiveness in treating intractable migraine.

To report the unique effectiveness of propofol, an intravenous anesthetic agent, in treating refractory migraines and other headaches in the setting of an outpatient headache center. We initially observed the dramatic abolition of ongoing migraine in patients (n=6) being treated with propofol in preparation for epidural and other nerve blocks in the headache and pain clinic. The reduction of headache severity was virtually 100%. We decided to treat an additional cohort of patients with intravenous propofol in the headache clinic; these patients had intractable migraines that were refractory to the usual abortive treatments. Subanesthetic doses of propofol were employed in this study. This is the first known report of the utility of this agent specifically for the treatment of intractable headache. Seventy-seven patients were treated for intractable headache in the clinic with intravenous propofol, for both migraine and nonmigrainous headache refractory to the usual methods of abortive treatment. The average reduction in headache intensity was 95.4% after an average of 20 to 30 minutes of intravenous propofol treatment, using a patient-rated visual analog scale of 0 to 10. Sixty-three of 77 patients reported complete abolition of their headache. The average dose of propofol was 110 mg, which is well within the usual range of preanesthetic doses and is clearly subanesthetic. Moreover, only three of the treated patients reported a return of the headache on the day following treatment. The neuropharmacology of propofol and the putative multiple mechanisms of action upon various neurotransmitter systems in the brain, particularly gamma aminobutyric acid A receptor subtypes, are discussed to explain the results in our patients. The use of intravenous propofol may represent a new, rapid, and highly effective form of abortive headache treatment in the headache clinic or emergency room setting and may offer an alternative to other treatment modalities for acute migraine and other severe intractable headaches. The effectiveness of propofol raises many new questions about the pathophysiology of migraine and other headaches.

Wirkungsvergleich von Propofol in drei subhypnotischen Dosierungen im Rahmen der Tumor-Chemotherapie

In anaesthesia and critical care propofol is often used as a hypnotic or sedative. There are some reports showing propofol as a mood-altering drug. The use of propofol in subanaesthetic doses, for example in antineoplastic chemotherapy, led to similar results. In previous studies it was hypothesised that these mood effects could also reduce chemotherapy-induced nausea and vomiting. The present prospective randomised double-blind study evaluated mood effects of different subanaesthetic doses of propofol in oncology patients who received antineoplastic chemotherapy. Propofol was applied in a double-blind and randomised manner as follows (N = 8 per group): Initial bolus of 0.1 mg/kg followed by a continuous infusion of 1.0 mg/kgxh (group 1), 1.5 mg/kgxh (group 2) or 2.0 mg/kgxh (group 3). Dependent variables were as behavioural (i.e. nausea and vomiting) as aspects of mood as somatic aspects. Subanaesthetic doses of propofol showed different effects. In respect of somatic variables some well-known results were replicated, showing highest reduction of blood pressure under highest dose of propofol. With regard to psychic variables no deterioration of mood or feeling tone was seen. Rather, a reduction of anxiety and especially under 2.0 mg/kgxh an induction of well-being occurred. However, even propofol was used as the only "anti-emetic" drug, patients reported no induction of nausea and vomiting during antineoplastic chemotherapy. Further studies are needed to specify the "anti-emetic" effects of subhypnotic propofol in antineoplastic chemotherapy. Especially a comparison with a standard drug for the prevention of nausea and vomiting, such as ondansetron, will have to be conducted. The results of this study showed that a dose of propofol of 1.0 mg/kgxh after an initial bolus of 0.1 mg/kg is a useful reference dose.

Propofol at conscious sedation doses produces mild analgesia to cold pressor-induced pain in healthy volunteers

Study objective: To determine whether subanesthetic doses of propofol have analgesic effects in healthy volunteers. Design: Prospective, double-blind, placebo-controlled, randomized, crossover trial. Setting: Human psychomotor performance laboratory within our anesthesia and critical care department. Subjects: 12, non-drug abusing volunteers, aged 22 to 38 years. Interventions: Five drug conditions were used in which a loading injection was followed by a 20-minute infusion period: placebo [saline (Intralipid)] injection, Intralipid infusion; propofol 0.125 mg/kg injection, propofol 12.5 mcg/kg/min infusion; propofol 0.25 mg/kg injection, propofol 25 mcg/kg/min infusion; propofol 0.5 mg/kg injection, propofol 50 mcg/kg/min infusion; fentanyl 1.4 mcg/kg injection (positive control), Intralipid infusion. Five minutes into the infusion period and 115 minutes after the infusion period was terminated, subjects immersed their forearms in ice-cold water for three minutes while pain assessments were recorded. Measurements and Main Results: Propofol at the two higher doses during part of the first immersion produced a significant reduction ( p < 0.05) in pain intensity and bothersomeness ratings. However, relative to fentanyl, the analgesia was mild. Propofol did not affect any ratings on the 15-item short-form McGill Pain Questionnaire, whereas fentanyl reduced 10 of the ratings. Conclusion: Our laboratory results are consistent with the commonly accepted clinical practice of supplementing propofol with an opioid in conscious sedation procedures to provide a satisfactory level of pain relief.