Treatment of status migrainosus by general anesthesia
Female patient, aged 50 years, with status migrainosus, in the last 5 days with visits to the emergency department, medicated parenterally with various agents without result. Without comorbidities, dehydrated, described her pain as “well over 10” in Visual Numeric Scale (VNS). After consulting the literature and given the apparent severity of the condition, we opted for a general anesthesia: induction with fentanyl, propofol, and vecuronium and maintenance with isoflurane and propofol for 2 hours. Following treatment, in the post anesthetic recuperation (PAR), the patient related her pain as VNS 3, and was released after 5 hours with VNS 2. Subsequently, her preventive treatment was resumed.
The most likely diagnosis of this patient is
The state migrainosus is a complication of migraine characterized by disabling pain crises, that lasts for longer than 72 h and is presented in a continuous manner without remission and unresponsive to usual treatments.1 It is a rare condition but always presents as an emergency and a challenge to primary care physicians. The risk of stroke and suicide attempts is part of the complications. The pathophysiology for this type of evolution is still controversial and due to the common failure of the usual treatment in such circumstances; various approaches in bouts of severe migraine with anesthetic drugs have been made, from local endovenous anesthetics to opioids, and also with hypnotics as propofol. This latter strategy has come to very interesting results, and this alleged action would be the interaction with the central GABA receptors,2 with an mechanism similar to other anesthetic agents, including inhaled isoflurane.2, 3, 4. Therefore, other drugs with similar mechanism of action also have been a target of research.5 Some of the doses of propofol proposed in the literature 6,7 were superior to those used in general anesthesia and, although intermittent, conducted to loss of consciousness and respiratory depression, reaching 7 a bi spectral index (BIS) of 40. Given these assumptions in the literature, we report a case in which a general anesthetic was successful in an attempt to abort a crisis of severe status migrainosus which was present in the last five days, after the failure of several attempts with the first-line therapy.
The patient has had several irregular treatments, and at that occasion was being preventively medicated with amitriptyline 25 mg at night and atenolol 50 mg in the morning. During crises, the patient used triptans; in her visit, we suspected of abuse of that last medication. At that time, she was in a crisis of 5 days duration, and unresponsive to all treatment attempts, with several passages in the emergency department, with use of intravenous dipyrone 1 g, dexamethasone 4 and 8 mg, chlorpromazine 25 mg, haloperidol 5 mg, ketoprofen 100 mg, meperidine 30 mg and 40 mg, lidocaine 100 mg, sodium valproate 100 mg, and antiemetics, some of them more than once, all without any satisfactory result; without food for three days, no vomiting, but had nausea and photophobia, was dehydrated and described her pain, with difficulty, as “far superior” to 10 in the Visual Numeric Scale (VNS)! 8,9
Given the failure of previous therapies, the description in the literature of drugs, doses and procedures which, in the view of an anesthesiologist, configured an approach that practically was an anesthesia, even with loss of consciousness and airway obstruction, and that were conducted in an induction of anesthesia ward or anesthesia recovery room with all available and habitual anesthetic monitoring present, we considered to accomplish a general anesthesia as a last attempt to stop the pain status.
Blood pressure was 150 × 90 mm Hg, heart rate = 104 bpm, with no other noteworthy findings. The patient was taken to the operating room, with ECG monitoring with similar DII, pulse oximetry and noninvasive blood pressure determination.
The patient was inducted with fentanyl 200 μg, propofol 150 mg and vecuronium 7 mg after ventilation by mask with O2 100%. The patient was intubated and underwent controlled mechanical ventilation keeping saturation always above 98% and capnometry with values 34-36 mmHg. Maintenance of anesthesia was performed with isoflurane 0.5% in oxygen 40% and continuous infusion of propofol 1 mg kg−1 h for 2 hours. The patient remained hemodynamically stable throughout this period. After that, the patient was decurarized, awakened, extubated and taken to the postanesthesia recovery room. Once the first contact was possible, the patient quantified and described considerable improvement in headache and rated pain as VAS = 3. After 5 hours, the patient was discharged. Before that, the patient drank water, remained without nausea and rated pain as VNS = 2. A week after discharge, the patient reported that headache had stabilized, with a pattern alike the circumstances preceding the status migrainosus crisis, which allowed the reintroduction of the usual preventive medication by attending doctor.
It is estimated that migraine has a prevalence of 15% in general population 8; of which 1.4–2.2% is present as chronic migraine, 9 that, in adulthood, affects women twice, as compared with men.10
The treatment of migraine is targeted at relieving the symptoms by administrating analgesics, nonsteroid anti-inflammatory drugs, ergot alkaloids, triptans, antiemetics and opioids. Status migrainosus is a complication of its evolution and, although considered rare, a prospective study11 of 2006 showed that at some point of their lives about 20% of patients with chronic migraine experienced pain for longer than 72 h. Modifications of neurotransmission occur in migraine and studies showed that these patients have an alteration in the metabolism of serotonin (5-HT). Potent agonists of 5-HT receptors with antimigraine activity have their effects explained by the reduction of vasogenic inflammation and partly by the vasoconstrictor effects on meninges, upon stimulation of 5-HT receptors.7 By 1985, it was demonstrated that GABA would exert an inhibitory control over serotonergic neurons12 and that drugs effective in fighting migraine have their effects mediated by the agonism of GABAa receptors, increase of GABA in the brain and decrease in the frequency of stimulation of the dorsal raphe serotonergic cells.13
Propofol is a hypnotic agent for use in anesthetic procedures, have antiemetic properties and its efficacy has been demonstrated in cases of severe migraine. This agent would act through its agonist activity at the GABAa receptor subunits β1, activating chloride channels and inhibiting synaptic transmission.7 Opioids are agents that provide relief from pain, and are widely used in anesthesia and often in great number of painful conditions. Then, their use in refractory migraine is not surprising. Their continued use is, however, a matter of controversy. The GABAa sub receptor is an important target of inhalational anesthetics,18 and these drugs, as well as intravenous agents, stimulate the receptor 19,20 in a mechanism similar to that of drugs currently studied for the treatment of migraine, which justifies this mention in the literature5 and the interest in this case. General anesthesia with propofol, fentanyl and isoflurane was an extreme option in an extreme case unsolved for a several days, and its use had its foundations with the knowledge of literature, and should be investigated further for more definitive conclusions.
Status migrainosus is a rare disabling complication and anesthetics have been the subject of research in its treatment; the option for general anesthesia with agents that stimulate GABA receptors, propofol and isoflurane, in association with fentanyl, proved effective and should encourage new research.
- International Headache Society. The international classification of headache disorders Cephalalgia (Suppl. 1) (2004), pp. 1–150
- J.C. Krusz, V. Scott, J. Belanger. Intravenous propofol: unique effectiveness in treating intractable migraine Headache, 40 (2000), pp. 224–230
- A.C. Hall, W.R. Lieb, N.P. Franks. Stereoselective and non-stereoselective actions of isoflurane on the GABAA receptor. Br J Pharmacol, 112 (1994), pp. 906–910
- C. Vahle-Hinz, O. Detsch, M. Siemers, et al. Local GABA(A) receptor blockade reverses isoflurane's suppressive effects on thalamic neurons in vivo. Anesth Analg, 92 (2001), pp. 1578–1584
- Krusz JC, Scott V, Belanger J. Intravenous propofol: unique effectiveness in treating intractable migraine. Headache.2000;40: 224-30.
- Mendes PM, Silberstein SD, Young WB, Rozen TD, et al. Intravenous propofol in the treatment of refractory headache. Headache. 2002;42:638-41.11.
- Drumond-Levis J, Scher C. Propofol: A New Strategy for Refractory Headache. Pain Med. 2002;3: 366-9.12.
- Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries1990-2010: a systematic analysis for the Global Burden of Dis-ease Study 2010. Lancet. 2012;380:2163-96.
- Natoli JL, Manack A, Dean B, et al. Global prevalence of chronicmigraine: a systematic review. Cephalalgia. 2010;30:599-609.
- Nappi RE, Sances G, Detaddei S, et al. Hormonal management of migraine at menopause. Menopause. 2009;15:82-6.
- Pryse-Phillips W, Aubé M, Bailey P, et al. A clinical study ofmigraine evolution. Headache. 2006;46:1480-6.
- Nishikawa T, Scatton B. Inhibitory influence of GABA on centralserotonergic transmission. Involvement of the habernulo-raphepathways in the GABAergic inhibition of ascending cerebralserotonergic neurons. Brain Res. 1985;331:91-103
- Mathew NT, Kailasam J, Meadors L, et al. Intravenous valproatesodium (depacon) aborts migraine rapidly: a preliminar report.Headache. 2000;40:720-3
- Cutrer FM, Moskowitz MA. Wolf Award 1996. The actions ofvalproate and neurosteroids in a model of trigeminal pain.Headache. 1996;36:579-85.21.
- Saper JR, Lake 3rd AE, Hamel RL, et al. Daily scheduled opioidsfor intractable head pain: long-term observations of a treat-ment program. Neurology. 2004;62:1687-94.23.
- Rothrock JF. Treatment-refractory migraine: the case for opioidtherapy. Headache. 2008;48:850---4.8.
- Headache Toolbox (editorial) --- Opioid therapy for migraine.Headache. 2007;47:1371-2
- Hall AC, Lieb WR, Franks NP. Stereoselective and non-stereoselective actions of isoflurane on the GABAA receptor. BrJ Pharmacol. 1994;112:906-10.
- Krasowski MD, Koltchine VV, et al. Propofol and otherintravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that forisoflurane. Mol Pharmacol. 1998;53:530-8.
- Olsen RW, Li GD. GABA(A) receptors as molecular targets of gen-eral anesthetics: identification of binding sites provides clues toallosteric modulation. Can J Anaesth. 2011; 58:206-15.