2011 Jul-Sep;7(3):331-5. doi: 10.4103/0973-1482.87039. Pharmacologic Interventions for Stroke | Stroke CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial. Uncrossmatched packed red blood cells are an initial resuscitative fluid choice that is often used in hypotensive trauma patients, with a goal to maintain SBP 90 mmHg in patients suspected of having a TBI. Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring. J Am Coll Cardiol. Aurora Zangh, Sebastiano Cimino, Daniele Urz, Salvatore . Pseudobulbar Affect: Considerations for Managed Care Professionals, Safety, Tolerability, and Efficacy Results Trial of AVP-923 in PBA Investigators. Among the most frequently reported AEs, falls, dizziness, and diarrhea occurred at a higher rate in the dextromethorphan/quinidine groups compared with placebo.29 Urinary tract infection was also reported at a higher frequency in the dextromethorphan/quinidine 30/10-mg group compared with placebo.29. Accessed October 2, 2017. Similarly, 60 mg daily of fluoxetine for 3 months was shown to be effective in the treatment of obsessive-compulsive disorder caused by brain injury. 6. Epub 2018 May 1. Holcomb JB, Tilley BC, Baraniuk S, et al. Endoscopic retrograde cholangiopancreatography or cholecystectomy first in patients with suspected choledocholithiasis? Surgery is a mainstay of treatment for HGG, although it is not curative, and adjuvant therapy is required. Currently, the evidence suggests neurocognitive or neurobehavioral deficits, particularly cognition difficulties and agitation, are primary indications for amantadine use.[26,29,30]. Acosta-Escribano J, Fernandez-Vivas M, Grau Carmona T, et al. Zafonte R, Watanabe T, Mann N. Amantadine: A potential treatment for the minimally conscious state. 20. Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study. Management of the minimally responsive patient. 1984;35(1):503-511. doi: 10.1146/annurev.me.35.020184.002443. Inaba K, Menaker J, Branco BC, et al. 46. Careers. Although insufficient evidence exists to establish guidelines for optimal pharmocotherapy, medications may be used to support recovery. Pharmacotherapeutic management of lower urinary tract symptoms 24. 1998;12(suppl 4):S5-S20. Schadel M, Wu D, Otton SV, Kalow W, Sellers EM. We suggest that patients with ICP 2129 for at least 30 minutes, 3039 for at least 15 minutes, or 40 or more for 1 minute who have met sodium and osmolality thresholds (i.e., on maximal hyperosmolar therapy) are candidates for pentobarbital coma. Ahmed A, Simmons Z. Pseudobulbar affect: prevalence and management. We are experimenting with display styles that make it easier to read articles in PMC. Balakrishnan P, Rosen H. The causes and treatment of pseudobulbar affect in ischemic stroke. Miller A, Pratt H, Schiffer RB. The majority of studies suggest that SSRIs improve neurobehavioral, neurocognitive, and neuropsychiatric deficits, specifically agitation, depression, psychomotor retardation, and recent memory loss; however, most data originates from nonrandomized trials. The reader is referred to a review article from 2013 that suggests an approach to the management of the bleeding patient on a novel anticoagulant, which may be extrapolated to the head-injured patient. Pharmacists can also help patients and family members to identify activities or factors that exacerbate symptoms, such as anxiety or excessive stress. Hummel TR, Salloum R, Drissi R, Kumar S, Sobo M, Goldman S, Pai A, Leach J, Lane A, Pruitt D, Sutton M, Chow LM, Grimme L, Doughman R, Backus L, Miles L, Stevenson C, Fouladi M, DeWire M. J Neurooncol. N Engl J Med. When managing the immediate and long-term consequences of such injuries, clinicians have many pharmacological options, including psychostimulants, antidepressants, antiparkinsonian agents, and anticonvulsants. 41. Decompressive craniectomy for elevated intracranial pressure and its effect on the cumulative ischemic burden and therapeutic intensity levels after severe traumatic brain injury. Small molecule inhibitors in children with malignant gliomas. Arciniegas DB, The cholinergic hypothesis of cognitive impairment caused by traumatic brain injury. J Neuropsychiatry Clin Neurosci 2002;14:202-205. Drugs.com website. When considering long-term pharmacotherapy for seizure management, attention should be paid to the risk of recurrent seizures and seizure type when deciding to initiate AEDs and choosing a drug. The acute care surgery model: managing traumatic brain injury without an inpatient neurosurgical consultation. Clinical review: Traumatic brain injury in patients receiving antiplatelet medication. Although CPP may not be an ideal surrogate for cerebral blood flow and metabolic delivery, other modalities have not gained widespread use due to paucity of strong data. Phelan HA. The BC Medical Journal is a general medical journal published by Doctors of BC. Valproic acid, for example, enhances inhibitory control mediated by the neurotransmitter GABA, thereby promoting general central nervous system stabilization, but findings thus far have been mixed. This activity will update pharmacists and other healthcare professionals on current treatments for pseudobulbar affect (PBA). Patients were randomized to either placebo or 2 doses of dextromethorphan/quinidine, 30/10 mg or 20/10 mg, dosed twice daily. J Head Trauma Rehabil 2002;31:300-313. Basic labs are ordered to evaluate for coagulopathy and seizure prophylaxis is started (discussed below). In vitro norepinephrine significantly activates isolated platelets from healthy volunteers and critically ill patients following severe traumatic brain injury. Review of available studies of the neurobiology and pharmacotherapeutic CNS Spectr. Rudolph JL, Fonda JR, Hunt PR, et al. Open or continuous EVD have been associated with better ICP lowering than intermittent or closed EVD, although EVD monitors have not been shown to be superior to intraparenchymal ICP monitors. 2008;10(3):216-222. Basak R, Bentley JP, McCaffrey DJ, Bouldin AS, Banahan BF. J Trauma. Work SS, Colamonico JA, Bradley WG, Kaye RE. [26] It is also a noncompetitive NMDA receptor antagonist and may provide protection against possible glutamate-mediated excitotoxicity in the context of TBI. In addition, patients treated with amantadine demonstrated changes in outcome LOC, specifically improved arousal and LOC as measured by the Glasgow Coma Scale. [22] Finally, paroxetine or citalopram, at a dose of 10 to 40 mg daily, was shown by another study to be equally effective in the treatment of pathological crying. J Psychopharmacol. Pharmacists also have a role in advising prescribers on appropriate off-label uses of drugs.50 In situations where patients are unable to swallow whole capsules, pharmacists may also use their expertise to compound liquid formulations of, for example, dextromethorphan and quinidine, as a suspension.51, Assist Patients/Caregivers With Coping Strategies for Living With PBA. Forsyth R, Jayamoni B. Noradrenergic agonists for acute traumatic brain injury. 2016 Aug;17(8):42. doi: 10.1007/s11864-016-0418-0. 2013;8(8):e72232. High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens. Multiple studies of amantadine at a dose of 100 to 300 mg daily have suggested its effectiveness in both the acute and chronic care phases after TBI, particularly in diffuse, frontal, or right-sided brain injury. 78 . 11. Mayo Clin Proc 2000;75:711-721. Blackwell B. There are also a number of animal studies examining drugs that have the potential to adversely affect brain recovery following TBI. Fortunately, a number of pharmacological interventions show promise in helping patients cope with these losses and deficits. Funding Sources: MBP is supported by National Institutes of Health (Bethesda, MD) NHLBI R01 HL111111 and NIGMS R01 GM120484. 34. 25. Gunshot wounds to the head are the most lethal of injuries, but, due to overall incidence, result in less total deaths.3,4, The primary insult to the brain cannot be undone and results in brain tissue damage, impaired cerebral blood flow (CBF) regulation, and alterations in brain metabolism with upregulation of inflammatory mediators, oxidative stress, and vasospasm. Wroblewski B, Leary J, Phelan A, et al. Psychopharmacology (Berl). Wright DW, Yeatts SD, Silbergleit R, et al. 23. [Scandinavian guidelines for prehospital management of severe traumatic J Neurotrauma 31, 135-158. 43. Epilepsia 2003;44:2-10. The AAN recommended that if approved by the FDA, and the AEs were acceptable, dextromethorphan/quinidine should be considered for symptoms of pseudobulbar affect in patients with ALS as a Level B recommendation.41 In addition, the AAN 2014 guidelines on the assessment and management of psychiatric disorders in individuals with MS recommended that dextromethorphan/quinidine is possibly effective and safe and may be considered for treating individuals with MS with PBA (Level C, 1 Class 2 study).42, Dextromethorphan/quinidine is likely to be administered to patients for extended periods of time in chronic and progressive neurological diseases, such as AD, MS, and PD, and it is essential that a long-term safety profile is favorable. Trends Pharmacol Sci. 37. Joseph B, Hadjizacharia P, Aziz H, et al. Joseph DK, Dutton RP, Aarabi B, Scalea TM. 2016;21(S1):34-44. Am J Psychiatry. In the majority of studies, methylphenidate has been administered twice daily, either at a fixed dose of 10 to 15 mg or at a dose of 0.3 mg/kg. The rehabilitation of patients with traumatic brain injury. Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: A pilot double-blind randomized trial. The in vivo effect of propranolol on cerebral perfusion and hypoxia after traumatic brain injury. Davis DP, Hoyt DB, Ochs M, et al. 45. Schallert T, Hernandez T, Barth T. Recovery of function after brain damage: Severe and chronic disruption by diazepam. This site needs JavaScript to work properly. PBA is an underrecognized and undertreated condition that affects upwards of 2 million individuals in the United States. 9. Neurology. Kim E, Humaran T. Divalproex in the management of neuropsychiatric complications of remote acquired brain injury. Walton SM, Schumock GT, Lee K-V, Alexander GC, Meltzer D, Stafford RS. Traumatic Brain Injury (TBI) Management LITFL CCC De Marchi R, Bansal V, Hung A, et al. [27], Bromocriptine is a dopamine receptor agonist affecting primarily D2 receptors and to a lesser extent D1 receptors. Pharmacotherapeutic management of pseudobulbar affect. Clinical features and basic mechanisms of quinidine-induced arrhythmias. Effect of head elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients. Reversal of shock through intravenous fluids and vasopressors while avoiding harm from volume overload is the first step in management of AKI. Adv Ther. Surgery is also the mainstay for LGG. 2008;44(9):661-668. doi: 10.1358/dot.2008.44.9.1258664. Schneider W, Drew-Cates J, Wong T, et al. CPP is defined as mean arterial pressure (MAP) intracranial pressure (ICP). J Head Trauma Rehabil 1987;2:29-33. Arch Phys Med Rehabil 1993;74:153-160. Intraparenchymal monitors are placed directly into brain tissue but may not accurately measure pressure in the CSF due to pressure gradients that occur after TBI.5052 Both device types measure intracranial pressure, and the calculated CPP is used as a surrogate for CBF, and, by extension, brain oxygenation and metabolic supply. A 2013 study found that acute care surgeons can effectively manage patients with mild TBI without neurosurgical evaluation, although this cannot be firmly extrapolated to patients with moderate or severe TBI, and we suggest neurosurgical consultation for any intracranial hemorrhage, irrespective of neurologic function.48. drugs.com/price-guide/nuedexta. 1Chief Resident in General Surgery, Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Medical Center North, CCC-4312, 1161 21st Avenue South, Nashville, TN 37232-2730, ude.tlibrednav@allev.a.leahcim, 2Professor of Surgery, Division of Acute Care Surgery, Department of Surgery, University of Florida, Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, ude.lfu.xaj@lladnarc.eiraM, 3Assistant Professor of Surgery, Neurosurgery, Hearing & Speech Sciences, Division of Trauma, Surgical Critical Care, and Emergency General Surgery, Department of Surgery, Section of Surgical Sciences, Center for Health Services Research, Vanderbilt Brain Institute, Vanderbilt University Medical Center, 1211 21st Avenue South, Medical Arts Building, Suite 404, Nashville, TN 37212, ude.tlibrednav@letap.b.ruyam, Algorithmic Approach to the Management of Severe Traumatic Brain Injury (GCS <9), Simple algorithm for the management of severe head injury as described in the text. Clin Toxicol. Surgery is a mainstay of treatment for HGG, although it is not curative, and adjuvant therapy is required. Thomas SH, Orf J, Wedel SK, Conn AK. Treatment options include the off-label use of centrally acting drugs, such as antidepressants, and the FDA-approved drug combination of dextromethorphan and quinidine. eCollection 2022. Traumatic acute subdural hematoma: major mortality reduction in comatose patients treated within four hours. Exposure to these drugs can increase substantially when coadministered with dextromethorphan/quinidine. In this review, we summarize the current state of the . Accessed October 2, 2017. 1981;21(3):201-219. doi: 10.2165/00003495-198121030-00002. Bookshelf Massagli T. Neurobehavioral effects of phenytoin, carbamazepine, and valproic acid: Implications for use in traumatic brain injury. Saletu B, Saletu M, Grunberger J, et al. Elevated ICP should be managed in an algorithmic fashion utilizing simple beside maneuvers, hyperosmolar agents, ventricular drainage, barbiturates, and operative intervention when appropriate. 7. With appropriate education, pharmacists can play an important role in the education, assessment, and monitoring of pharmacologic treatments for PBA that can potentially result in better outcomes. An official website of the United States government. A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury. Longer-term safety of dextromethorphan/quinidine treatment of PBA was investigated in an open-label, 52-week, multicenter study.43 A total of 553 patients were recruited (40.3% had MS; 31.8%, ALS; 8.3%, stroke; 3.8%, TBI) and were treated with dextromethorphan/quinidine 30/30 mg twice daily.43 The most frequent AEs during treatment were nausea (24.8%), headache (22.8%), dizziness (19.5%), falls (16.5%), diarrhea (16.3%), fatigue (14.6%), and weakness (13.7%).43 These long-term AEs are consistent with results observed in placebo-controlled trials. Pharmacologic venous thromboembolism prophylaxis after traumatic brain injury: a critical literature review. Breathing should be optimized to maintain oxygenation and prevent ventilatory dysfunction, as extremes in CO2 can lead to cerebral vasoconstriction, vasodilation, and have been shown to be predictors of morbidity and mortality.8 Hyperventilation is used by some providers to acutely decrease ICP through hypocarbic vasoconstriction, despite evidence showing an association between even brief periods of hyperventilation and increased mediators of secondary brain injury in areas adjacent to injured brain tissue as well as local reductions in cerebral perfusion.1618 This strategy should be used with caution, and perhaps only employed to acutely combat signs of active herniation while initiating more definitive treatment. Brailowsky S, Knight RT, Efron R. Phenytoin increases the severity of cortical hemiplegia in rats. 2017 Oct; 97(5): 10151030. Pharmacotherapeutic Management of Neuropathic Pain in End-Stage Renal Adequate fluid resuscitation, reversal of coagulopathy, maintenance of cerebral perfusion, and treatment of intracranial hypertension are common interventions early in the treatment of TBI. 14. [Europe PMC free article] [Google Scholar] Dienel GA, 2014. Cohen MJ, Brohi K, Ganter MT, Manley GT, Mackersie RC, Pittet JF. Medical Journals N Engl J Med 2005;352:2043-2047. 11. 1997;63(1):89-93. doi: 10.1136/JNNP.63.1.89. Other factors that deserve important consideration in the acute management of TBI patients are venous thromboembolism, stress ulcer, and seizure prophylaxis as well as nutritional and metabolic optimization. Ferraro L, Antonelli T, Tanganelli S. The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: Prevention by local GABAA receptor blockade. Currently, we cannot reverse the initial insult causing a TBI, referred to as the primary injury. A systemic review of randomized controlled trials of hypothermia in traumatic brain injury found that hypothermia was associated with reduced mortality and improvements in neurologic function.73 Other authors call into question the benefits of hypothermia in TBI citing poor quality trials.74 The BTF currently recommends against the routine use of early, short term prophylactic hypothermia in patients with diffuse TBI.30, Patients with traumatic brain injury are at risk for venous thromboembolic disease given venous stasis, venous injury, and potential coagulopathy associated with TBI. Pharmacotherapeutic Management of Pseudobulbar Affect - AJMC Pharmacologic agents are often withheld in the initial post-injury period over concerns for worsening of an intracranial bleed. Dr Waxman is a psychiatry resident at the University of Toronto. official website and that any information you provide is encrypted Anticholinergic effects include blurred vision, constipation, dry mouth, memory impairment, and urinary retention.14 Other adverse AEs include sedation and drugdrug interactions (eg, cytochrome P450 2D6 inhibitors can increase levels of TCAs).1,11 In addition, the potential cardiac risks of QT prolongation, orthostasis, and tachycardia may also constrain the prescribing of TCAs for PBA.14-17 For treatment of PBA, the dose ranges of the TCAs commonly used for PBA (eg, amitriptyline, imipramine, and nortriptyline) are listed in Table 1.3,8,18, Selective serotonin reuptake inhibitors (SSRIs) are also used off label for the treatment of PBA. 48. 19. For example, in TBI or stroke, the need for treatment may diminish as recovery occurs and neurological function is restored. The content of this field is kept private and will not be shown publicly. 4. Simple maneuvers like loosening of the cervical collar, raising the head of bed >30 degrees or maintaining a reverse Trendelenburg position (if no contraindication), and optimizing sedation and analgesia can decrease ICP, although some of these may not improve CBF or CPP.49 Blood products can be given to keep INR <1.5 and platelets 100,000 to prevent further intracranial bleeding, although these are arbitrary hemostatic thresholds and may be influenced by pre-injury antiplatelet/anticoagulants, availability of thromboelastography (TEG), neurologic changes, imaging changes, and/or institutional culture. The role of secondary brain injury in determining outcome from severe head injury. Dr Wasserman is a psychiatry resident at the University of Toronto. 2012;102(1):72-80. doi: 10.2105/AJPH.2011.300187. Amantadine acts presynaptically to enhance dopamine release or inhibit its reuptake, and can act postsynaptically to increase the number, or alter the configuration of, dopamine receptors. Curr Opin Crit Care 2005;11:111-116. Prehospital hypoxia in these same patients was associated with a significant increase in mortality, and there was no difference in hypoxic episodes between patients intubated vs. those not intubated in the field.10 Similarly, prehospital rapid sequence intubation performed by paramedics in head injured patients with GCS <9 was associated with an increase in mortality. ISSN 2293-6106 (Online) Newer modalities in the management of such injuries include both drugs and therapeutic strategies. Curr Pharm Des. Paroxetine versus citalopram treatment of pathological crying after brain injury. Ferguson JM. Curr Med Res Opin. ODell MW, Riggs RV. Cardiovascular effects of tricyclic antidepressants. Mass lesions may require operative evacuation depending on size, exam findings, and ICP measurements. Rapid warfarin reversal in anticoagulated patients with traumatic intracranial hemorrhage reduces hemorrhage progression and mortality. Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. 37. 1. 21. Pharmacotherapeutic management of pseudobulbar affect 32. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Weiner GM, Lacey MR, Mackenzie L, et al. 7,18 Dexmedetomidine has been shown to successfully reduce the shivering threshold in healthy volunteers. Neuropsychiatric symptoms may present as mood disorders, posttraumatic stress disorder, and personality changes characterized by disinhibition and egocentricity. Falls (35%) and motor vehicle collisions (17%) are the most common, with motor vehicle collisions leading to majority of fatalities. as described in part 1, patients with pseudobulbar affect (pba) experience episodes of involuntary and uncontrollable crying and/or laughing outside of socially appropriate circumstances. of Medical Journal Editors (ICMJE) recommends the following citation style, which is the now nearly universally The difference in oxygen content between blood entering and leaving the brain can be calculated to provide a global picture of supply and demand. Neuroanatomy of pathological laughing and crying: a report of the American Neuropsychiatric Association Committee on Research. looked at 812 head injured patients, about half of whom received pharmacologic prophylaxis (the majority with heparin). The outcome of patients with severe head injuries treated with amantadine sulphate. 15. Head trauma is the cause the death for many young persons. 4. 2011 Mar;70(3):535-46. doi: 10.1097/TA.0b013e31820b59de. Rosen H. Dextromethorphan/quinidine sulfate for pseudobulbar affect. Bookshelf 2013;9:483-489. doi: 10.2147/TCRM.S53906. 2006;185(10):544-548. When treating neurological deficits medically, there is evidence to support the tailored use of these agents for particular TBI clinical scenarios. Recent level II recommendations from the Eastern Association for the Surgery of Trauma (EAST) suggest obtaining a head CT scan in patients that present with suspected brain injury in the acute setting if it is available. 2007;151(6):737-748. doi: 10.1038/sj.bjp.0707253. Am J Phys Med Rehabil 1997;76:440-450. Cerebral microdialysis is a technique whereby a catheter is placed in the penumbra, or area adjacent to the traumatized brain, and used to evaluate the local biochemical environment. 38. [3], With advances in the management of head trauma, an increasing number of patients are surviving with residual neurological impairments. 18. Of the 283 patients who completed the trial, patients receiving the drug combination at either dose had lower daily episode rates of PBA compared with placebo; 46.9% and 49.0% lower rates in those treated with the 30/10-mg dose and 20/10-mg dose, respectively. You may notice problems with 47. Kasotakis G, Michailidou M, Bramos A, et al. The site is secure. J Clin Psychopharmacol. Introduction: Insomnia is a stress-related sleep disorder, may favor a state of allostatic overload impairing brain neuroplasticity, stress immune and endocrine pathways, and may contribute to mental and physical disorders. Basic pharmacology.
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