Markus Frey, MD

• Assistant Professor of Medicine
• Department of Cardiology and Angiology
• University of Freiburg
• Freiburg, Germany

The use of corticosteroids is limited by reported adverse consequences in 63% of patients medications joint pain purchase eldepryl canada. These effects include delayed wound healing symptoms low blood sugar generic eldepryl 5 mg with amex, hypopigmentation treatment yeast overgrowth purchase eldepryl online, dermal atrophy symptoms strep throat eldepryl 5 mg order on line, and scar widening [117] symptoms 9 days after iui best purchase eldepryl. Based on successful studies combining corticosteroid injections with 5-fluorouracil therapy and laser therapy, polytherapy may be the best method with which to use steroids, because lower dosing and fewer adverse effects occur [117,118]. Overall, an agent with global reduction in cell protein synthesis and proliferation is not ideal for achieving tissue regeneration. This therapy, which represents a middle ground between the low side-effect profile of 78 5. When given systemically, it has potent side effects though a longestablished safety profile. However, when combined with triamcinolone, the efficacy of local administration improved scar appearance in 50e96% of patients [119]. It may also be combined with surgery to reduce fibroproliferative scar recurrences. Unfortunately, most clinical trials recruit small numbers or are confined to populations inherently at risk for fibroproliferative scarring [120,121]. Imiquimod Originally marketed as a treatment for verruca, actinic keratosis, and basal cell skin cancer, imiquimod may be used in low-morbidity settings for the treatment of hypertrophic scars and keloids. This Toll-like receptor-7 agonist functions by stimulating dermal inflammatory cells to secrete interferons, ultimately recruiting activated leukocytes to skin when applied topically. This medication represents an exciting, minimally toxic, and targeted method of immune modulation with few systemic side effects, and mostly blistering or skin irritation as the major local side effect. A few small, randomized controlled trials evaluated the efficacy of imiquimod in the treatment of acute surgical incisions in the breast [124] and in minor dermatologic surgeries [124]. However, the most trials failed to show a difference in scar appearance and potentially may have worsened outcomes by potentiating inflammation [124]. In the case of already formed keloids and hypertrophic scars, imiquimod could be tested in select patients wishing to try nonsurgical therapies, but ultimately this product does not appear to have a role in acute wound healing. Laser Therapy In the 1990s, pulsed dye laser therapy emerged as a potential treatment for fibroproliferative and acute scars [125,126]. Like other disorders of aberrant proliferation, the mechanism proposed involves destruction of new blood vessels to limit, at a minimum, the erythematous appearance of some scars [126]. The idea behind targeting fibroproliferative scars with laser treatment comes from the principle that vascularity is partially responsible for their erythematous appearance. Although some case studies showed positive results in the treatment of keloids, the ischemic mechanism of keloid progenitor cell differentiation and proliferation is concerning [127]. Laser therapy has relatively few adverse effects (hyperpigmentation in 1e24% of patients and transient purpura in some). Bleomycin Another potent chemotherapeutic being used in dermal fibroproliferative disorders is bleomycin. In resistant hypertrophic scars, keloids, and warts, bleomycin has been used off-label by dermatologists via intradermal injections [129]. Similar to other off-label use products, there are few clinical trials testing its efficacy [129]. However, if monitored closely with an experienced practitioner, it may be effective and safe. Side effects from treatment with bleomycin may be as minor as skin irritation, to as severe as skin necrosis and eschar formation [129]. When giving systemically, bleomycin notoriously causes pulmonary and skin fibrosis in humans and mice [130]. As such, it is often used to induce both conditions in an effort to create mouse models of pulmonary fibrosis and scleroderma [130]. Like other chemotherapeutic agents exploited in wound healing, development of a targeted therapy would be more attractive. Silicone, in either sheets or gels, emerged in the 1980s as a potential vulnerary agent by providing a hydrating barrier to open wounds. For decades, silicone has been used in deeper tissues, in the form of breast implants or as an interface for matrices used in hernia repair and large tissue defects; which highlight its safety [131,132]. Its development came from a series of studies that implicated dehydration of deep dermal fibroblasts as the mechanism for inducing scar collagen production. This therapy has been studied for both treatment and prophylaxis of excessive scarring [133]. Initial studies showed conflicting results in terms of efficacy [134,135], requiring further study. A review emphasized the weak evidence surrounding the use of silicone gel sheets in the treatment of keloids and hypertrophic scars [136]. However, silicone gel sheets will likely continue to be used because they are a noninvasive treatment with few adverse effects. In clinical practice, silicones are usually found as a component to a complex matrix or as a topical therapeutic dressing for chronic wounds [132]. Although the efficacy is unknown, they are safe to continue using and investigating. Pressure Dressings and Negative-Pressure Wound Therapy Despite being in clinical use since the 1970s [137], pressure dressings have not been validated by experimental trials to be efficacious in prophylaxis or in the treatment of scars [138]. These treatments may be efficacious in reducing the appearance of a scar if used in polytherapy, but further investigation is warranted. Pressure earrings have been used in earlobe keloid excisions but have not been shown to eliminate recurrence. Most surgeons are familiar with this technique, in which a vacuum is applied to an open wound (chronic or acute) to activate mechanotransducers in cells and potentiate cell proliferation and eventual wound closure by secondary intention [139]. The application of negative pressure in wound therapy appears to be ever increasing, with promising results as a treatment for acute wounds [140], chronic wounds [141], burns [142], and for the closure of large contaminated incisions [143]. Many modifications have been made to the vacuum system, such as the application of silicone sheets or foam pads, which ultimately make minor improvements in the overall technology. Radiation Therapy Radiation therapy can also be used as an adjunct to surgical excision in the treatment of keloids. Mechanistically, it is thought to decrease collagen production by reducing fibroblast proliferation and neovascular bud formation. Radiation therapy is most effective for recurrent keloids if a single dose is given within 24 h of surgical excision, but studies have attempted short courses of radiation after healing with positive results, as well [144]. Radiation treatment appears to decrease recurrence rates after surgical excision from 45e100% to 16e27% of patients [145e147]. The magnitude of difference from these studies clearly highlights their limited power. One limitation of radiation therapy is that standardized dosing, fractionation, time period, and frequency after surgical procedures has not been developed. However, like many other studies in wound therapy, large, randomized, controlled studies are required to evaluate the role of radiation further in wound healing. Given the morbidity of radiation, this is not a popular method to reduce scar tissue formation. Cryotherapy Cryotherapy has been studied in conjunction with surgical excision to treat keloids and hypertrophic scars. Many of these studies are limited by small sample size and poor controls, but the largest study reported a 79. Cryotherapy is thought to decrease collagen synthesis and mechanically destroy scar tissue. Side effects include hypopigmentation and depressed atrophic scar formation [150]. This therapy can be used as an adjunct to surgery or as monotherapy, but studies question its efficacy in large recalcitrant keloids [151]. Acellular dermal matrices, human amniotic membranes, and porcine intestinal mucosa, which once were used for large incision closures and hernias, are also emerging in the market as wound healing adjuvants. These, too, can be combined with a number of additional therapies, from impregnated pharmaceuticals to cultured stem cells [153]. Generally, results are promising in the treatment of chronic and diabetic wounds [152]. Tension Offloading An important field of study in wound healing focuses on mechanical forces. There are multiple examples of pressure, suction, or stretch that result in rapid cell proliferation, as is seen with vacuum-assisted wound closure and pregnancy [139,154]. In adult wound healing, tension initiates a signaling cascade leading to the proliferation of local cells typically in a symmetric pattern. Both keratinocytes and fibroblasts have mechanosensors imbedded in their cell membrane. In the case of fibroproliferative wounds, this may be an inciting factor leading to aberrant cell growth [139]. In fetal wound healing, the loss of dermal architecture leads to the deposition of actin protrusions that will contract and recruit local cells to close gaps in tissue and eventually regenerate lost structures [156]. This is perhaps the most stark difference in wound healing between prenatal and postnatal organisms, in which similar filaments and structures are involved but ultimately are used in entirely different ways [156]. On the back, chest, sternum, and tibia, incisions naturally stent open and can be predisposed to prolonged healing, infection, and dehiscence whereas areas with low tension and redundant tissue, such as the eyelid, heal with minimal scarring. A clinical trial tested an external tension offloading device known as "embraceÒ " in acute scar revision [157]. During this time, scars can lose their dark pigmentation, flatten, soften, and contractures can lessen. Because scars can often behave unpredictably, surgery is usually reserved until after this period has passed. There are many options for surgical treatment for scarring, including excision with direct closure, local skin flap coverage, or more extensive vascular flap coverage. These treatments are generally considered before surgical treatment or as an adjunct. For fibroproliferative scars, surgical treatment is usually a simple excision, with or without flap closure, depending on the size of the resulting defect. In chronic wounds, burns, and pressure ulcerations, surgery may consist of creating local or pedicled tissue flaps, split-thickness skin grafts, or repeated surgical debridements to encourage healthy wound healing. Studying the signals influencing cell polarity and differentiation, however, has been more fruitful. It is likely that if signaling cascades are targeted specifically via receptor agonists and antagonists, polytherapy will be needed to circumvent redundancies in the inflammatory pathway and signals leading to collagen deposition. Targeting Gap Junctions and Connexins Gap junctions are hypothesized to function during wound repair by transferring injury signals from cell to cell, coordinating the inflammatory response, mediating wound closure, and regulating scar tissue formation in response to injury [46,159e161]. Many connexins (Cx) are present in the skin; the most extensively studied connexin is Cx43, which is expressed in both the epidermis and dermis [76]. Cx43 has decreased expression at the wound edge by the first 1 or 2 days after injury [159]. During wound repair, increased phosphorylation of Cx43 by protein kinase C may cause decreased gap junctional communication through a decrease in unitary channel conductance. This inhibition then initiates the injury-related response by the involved cell, which recognizes injury via reduced cell-to-cell communication [162]. When Cx43 antisense oligonucleotides were applied to mouse skin wounds, decreased inflammatory cell infiltration, fibrotic tissue deposition, and accelerated wound healing were observed [163]. Other studies showed that transient inhibition of Cx43 decreases scarring after burn injury in wild-type mice and increases reepithelialization after burn injury in human diabetic patients [163,164]. To further support these data, Cx43 knockouts have accelerated wound closure [165] and decreased collagen type I synthesis in the presence of chemicals that uncouple communication between cells. Based on these data, the application of lithium chloride, a substance known to enhance signal propagation through gap junctions, produced the opposite effect: enhancing the deposition of granulation tissue, increasing open wound closure time, and increasing scar [166]. Given the strong correlation between Cx inhibition and improved wound healing, other therapies aimed at blocking signal transduction from cell to cell are under investigation. Through further investigation, researchers found that this peptide interacts with more than one portion of Cx43 and enhances cutaneous wound healing through decreased inflammation and scarring [160]. The advantage of this novel protein is that overall Cx43 expression is not altered. Moreover, the expression of other genes is not directly altered, unlike with antisense therapy and gene knockdown modalities. Other Drugs and Biologics Additional strategies increase the expression of intrinsic antiscarring molecules at the wound site, including fibromodulin, hyaluronic acid, and hepatocyte growth factor [168e170]. Stem Cells True skin regeneration at sites of injury has not been accomplished by single moleculeespecific therapy. The discovery of specific embryonic cells that self-renew indefinitely in culture and can generate an entire organism 82 5. Representation showing general principles of two cell-based therapeutic methodologies: (1) application of stem celleconditioned media, and (2) direct application of stem cells to the wound bed. It was immediately recognized that these cells held the potential to be used for regenerating dysfunctional organs and tissue. Equally obvious were the potential ethical problems related to using cells from human embryos. Several patients experienced improvements in visual acuity up to 12 months after treatment, a result that would not be expected in the absence of treatment. However, human spinal cord injury patients treated with similar cells in a phase I trial showed no improvement after treatment [187]. These results highlight that promising results in animal models are not easily translated to human applications, and that novel stem cell therapies must be tested rigorously in human trials. Based on their ability to expand in vivo and differentiate into multiple mesenchymal tissue types, these cells are thought to be an ideal source of autologous stem cells used for promoting wound healing and/or scar-reducing therapies [189].

Algorithms for out-of-hospital management of patients with decreased level of consciousness need to take these limitations into account while supporting optimally a relatively wide differential of underlying etiologies medicine wheel native american cheap eldepryl 5 mg buy online. One problem that is frequently encountered is the tendency for paramedics in the field to intubate almost any patient with impaired consciousness "to protect the airway symptoms renal failure discount eldepryl 5 mg line. Because intubation usually involves giving patients sedative and paralytic drugs medicine over the counter buy discount eldepryl, the in-hospital evaluation of the patient requires either relying on the paramedic exam or stopping the drugs and waiting for them to clear treatment laryngomalacia infant generic eldepryl 5 mg with visa. Initial assessment should therefore focus on determining if the out-of-hospital assessment/ treatment was adequately provided so that this is not merely repeated medicine 5277 purchase online eldepryl, causing delay in more advanced treatment. In addition to stabilization of vital functions of the patient, diagnostic and interventional steps should be initiated as early as possible, taking the underlying cause of impaired consciousness into account. The 7 Initial Management of Patients with Stupor and Coma 309 primary injury linking consciousness and lifesupporting vital body functions may either be directly in the cardiovascular or respiratory system. All patients need to be screened and continuously monitored for development of cardiovascular and respiratory decompensation. In the out-of-hospital setting, diagnosis of cardiovascular and respiratory compromise typically consists of assessment of heart auscultation to determine rate and rhythm, blood pressure measurements, lung auscultation, observation of the breathing pattern, and oxygen saturation. In addition to the tests introduced in the out-ofhospital setting, laboratory tests, imaging, and ultrasound are readily available in most emergency room and intensive care unit settings. This allows rapid diagnosis, for example, of free fluid in the abdomen raising concerns for intraabdominal bleeding in the trauma victim; pneumothorax for those with respiratory distress; or cardiac tamponade and function, as well as fluid status for those with hypotension. Initial evaluation of patients with impaired consciousness focuses on assessment and delivery of clinical interventions that are a fundamental part of the cardiopulmonary resuscitation protocol: airway, breathing, and circulation. Ensure Oxygenation, Airway, and Ventilation Stuporous or comatose patients with inadequate respirations will rapidly acquire additional brain injury from lack of oxygen, have worsened impairment of consciousness from hypercarbia, and poor overall medical outcome from aspiration pneumonia. The initial focus needs to be an emergent assessment of the need for intubation, which can be categorized into a failure to oxygenate (assess skin color, check for cyanosis; if available and depending on the urgency of the respiratory decompensation, take into account pulse oximetry and arterial blood gas measurements), failure to ventilate (assess for excessive or inadequate work of breathing; if available and depending on the urgency, expiratory carbon dioxide and arterial blood gas measurements may be obtained), failure to protect the airway (to assess bulbar function, cough reflex and amount of secretions as well as presence of vomiting have to be weighed against each other), and anticipated neurological or cardiopulmonary decline. A protocol for assessment of the airway should take into account the risks and benefits to predict the level of airway difficulty as well as the ease of bag-mask ventilation. Depending on the clinical scenario, level of expertise, and availability of the equipment, basic or more advanced airway support may be necessary and available. Breathing support includes application of artificial breaths via mouth-to-nose or mouth-to-mouth, and use of respiratory aids such as bag-valve-mask or ventilator-assisted respiratory support. Once the decision for endotracheal intubation has been made, the rapid sequence intubation is preferred to secure the airway, particularly of patients with suspected elevation of intracranial pressure. Steps include elevation of the head of the bed, intravenous access (allowing administration of pressors and fluids), preoxygenation for up to 5 minutes, and pretreatment with intravenous lidocaine (1. Stabilization of the cervical spine and replacing the head-tilt/chin-lift maneuver with the jawthrust technique is crucial for patients with any suspected trauma or any other cause for cervical spine instability as these interventions may otherwise further worsen the neurological injury. It is important to monitor all comatose patients carefully for hypotension as this may be a complication from medications given during intubation and worsen the outcome of all neurologically injured patients, particularly those with ischemia. Vagal discharge may occasionally lead to bradycardia or cardiac arrest, particularly in hypoxemic patients. As a general rule, keeping the mean arterial pressure between 70 and 90 mm Hg may serve as a guide to provide adequate cerebral perfusion. Avoid hyperventilation in general but particularly if the underlying etiology is brain ischemia as this may cause cerebral vasoconstriction. If a patient shows signs of herniation, hyperventilation may be needed as an emergency temporizing measure. Supraphysiologic oxygen levels are frequently provided to comatose or stuporous patients but have the potential to worsen outcome following traumatic brain injury17 and cardiac arrest18 due to formation of reactive oxygen species and impairment of mitochondrial function. Once confirmed, the patient should be connected to the ventilator (basic ventilator settings: volume-cycled ventilation at 8 cc/kg of ideal body weight and a respiratory rate of 12­14 per minute, unless the patient is herniating or medical conditions, such as adult respiratory distress syndrome, require adjustments), a pulse oximeter should be placed, an arterial blood gas sent, and a chest radiograph ordered. Patients comatose from drug overdose or who are hypothermic have depressed metabolism and require less ventilation than awake individuals. All intubated patients should receive frequent chest physical therapy and suctioning of the airway, and many may need nebulizer treatments to loosen secretions. Sedation should be interrupted daily to assess spontaneous respiratory patterns and need for continued ventilation. The optimal timing of tracheostomy in critically ill patients with neurological injury, such as those with stupor or coma, is controversial but many will discuss this option with families between the first and second week following the injury. Control of the airway and safety of regular feedings can be considered temporary measures that secure patient safety during a vulnerable period that can be re-evaluated over time. Maintain the Circulation Adequate blood supply to end organs including the brain is only achieved with an intact circulation. Emergent assessment of adequate circulation is crucial and involves checking the pulse, heart rate, cardiac rhythm, and blood pressure. All pulseless patients are either already or will rapidly be comatose, and the primary treatment includes chest compressions (recommended ratio of 30:2 chest compressions to ventilations at 100 compressions/min). Severe hypotension in patients with a pulse seen in all forms of shock needs to be addressed rapidly as additional brain injury will occur if untreated, and the cardiovascular condition may rapidly progress if untreated. Treatments include intravenous fluids, vasopressors, transfusion of red blood cells or other products, and stopping a bleeding source. While treating the circulatory deficiency, the provider should focus actively on a search for the underlying cause as this may further guide the management. Hypotensive comatose patients with traumatic brain injury may also have a pelvic fracture resulting in hypovolemic shock from abdominal hemorrhage or have cardiac tamponade from chest trauma. However, damage to the brain above the level of the medulla does not cause systemic hypotension (see Chapter 2). In young, previously healthy patients, particularly those with depressant drug poisoning, a systolic blood pressure of 70­80 mm Hg is usually adequate. In general, it is not necessary and may be dangerous to treat hypertension initially unless diastolic pressure exceeds 120 mm Hg or the patient is actively bleeding for example from a vascular cause. The elevation of blood pressure may be a reflex response to vascular occlusion (see Chapter 2), and, unless this is excluded, reducing blood pressure could worsen brain ischemia. In an older patient with known chronic hypertension, do not allow the blood pressure to fall below previously accustomed levels because the relative hypotension may cause cerebral hypoxia. When indicated, a number of intravenous agents are available to treat hypertensive emergencies, including labetalol (20­80 mg bolus over 10 minutes) and nicardipine (2­10 mg/hr). Assessments should involve determination of the circumstances in which the patient is found. Emergency Neurological Examination of the Comatose or Stuporous Patient Once the vital functions have been protected, proceed with the history and examination. The examination of the unconscious patient is covered in detail in Chapter 2, but a brief reprise is included here with emphasis on the elements that need to be covered quickly while initiating therapy in an emergency setting. Although the coma exam is, by necessity, relatively brief, the examiner has the luxury of time in doing the assessment when the patient has been under the continuous observation of other physicians on the ward or in an intensive care unit. In the emergency department, it is often necessary to weave obtaining the history and examination with urgent interventions. This goal of this emergency examination, together with the history and vital signs, is to allow the provider to categorize the etiology of unresponsiveness into one of four major categories (Table 7. Implanted computer chips that give full medical information are currently available but are not yet in common use. Coma of sudden onset in a previously healthy patient usually turns out to be self-induced drug poisoning, subarachnoid hemorrhage, head trauma, or, in older persons, brainstem hemorrhage or infarction. Most examples of supratentorial mass lesions produce a more gradual impairment of consciousness, as do the metabolic encephalopathies. In the general physical examination, after assessing and dealing with abnormalities of vital signs, look for evidence of trauma or signs that might suggest an acute or chronic systemic medical illness or the ingestion of selfadministered drugs. Evaluate nuchal rigidity, but take care first to ensure that the cervical spine has not been injured. They have proved themselves to be easily and quickly obtained and to have a high degree of consistency from examiner to examiner. Incomprehensible speech refers to the production of word-like mutterings or groans. Respiratory Pattern the pattern is recorded as regular, periodic, hyperpneic, ataxic, or a combination of these. Respiratory rate is best determined in patients not being mechanically ventilated. Eye Opening Patients with spontaneous eye opening have some tone in the eyelids and generally demonstrate spontaneous blinking, which differentiates them from completely unresponsive patients whose eyes sometimes remain passively open. Though spontaneous eye opening rules out coma by our definition, it does not guarantee awareness. Some patients remaining in a vegetative state, who by definition show eye opening, have been shown postmortem to have total loss of the cerebral cortex (see Chapter 9). Eye opening in response to verbal stimuli means that any verbal stimulus, whether an appropriate command or not, produces eye opening. More severely braininjured patients demonstrate eye opening only in response to a noxious stimulus applied to the trunk or an extremity. The worst response, no eye opening, applies to all remaining patients except when local changes such as periorbital edema preclude examination. Verbal Responses Assessment of the verbal best response allows assessment of orientation implying awareness of self and the environment. The patient knows who he or she is, where he or she is, why he or she is there, and the year, season, and month. Confused conversation describes conversational speech with syntactically correct phrases but with disorientation and confusion in the content. Inappropriate speech means intelligible isolated words, which may Pupillary Reactions Pupillary reactions to an intense flashlight beam are evaluated for both eyes, and the better response is recorded; use a hand lens or the plus 20 lens on the ophthalmoscope to evaluate questionable responses. However, this must be interpreted in light of the baseline eye positions for that individual, as many people have congenital or acquired strabismus. Spontaneous Eye Movement the best response is spontaneous, orienting eye movements in which the patient looks toward environmental stimuli. Record roving conjugate and roving dysconjugate eye movements when present, and reserve a miscellaneous movement category for patients without orienting eye movements who have spontaneous nystagmus, opsoclonus, ocular bobbing, or other abnormal eye movement. Note that this procedure should not be done in a patient with a suspected psychiatric presentation who may be nonresponsive but awake. A normal (awake) response includes horizontal nystagmus with the rapid phase toward the nonirrigated ear, accompanied by severe vertigo and nausea. Corneal Responses Responses to a cotton wisp drawn fully across the cornea or-safer-sterile saline dripped onto the cornea are recorded as present, asymmetric (describe), or absent. Motor Responses these should be tested and recorded in all extremities and the strength noted as normal or weak. The best score is given to patients who obey commands; care should be taken to avoid interpreting reflex grasping as obedience. If a command evokes no response, apply a noxious stimulus gently but firmly to each extremity (compression of finger or toenail beds, or of Achilles tendon) and to the supraorbital notches or temporomandibular joints. Localizing responses indicate the use of an extremity to locate or resist a remote noxious stimulus. Asymmetries in sensation (neither arm moves toward stimuli on one side of the body) or motor response (one arm moves less toward both sides) may indicate lateralized damage to the ascending sensory or descending motor pathways and should be noted. A more primitive response consists of a nonstereotyped, rapid withdrawal from a noxious stimulus; this response often incorporates hip or shoulder adduction. An abnormal flexion response in the upper extremities is stereotyped, slow, and dystonic, and the thumb is often held between the second and third fingers. Abnormal flexion in the lower extremities (the reflex triple flexion response) sometimes can be difficult to distinguish from withdrawal. An abnormal extension response in the upper extremity consists of adduction and internal rotation of the shoulder and pronation of the forearm. Oculocephalic Responses these are evaluated in conjunction with passive, brisk, horizontal, and vertical head turning. Patients with normal waking responses retain orienting eye movements and do not have consistent oculocephalic responses. Full oculocephalic responses are brisk conjugate eye movements opposite to the direction of turning. Abnormal responses, which may include selective loss of horizontal or vertical movement of one or both eyes, should be described. Remember, do not test oculocephalic reflexes in patients suspected of having sustained a neck injury. Caloric Vestibulo-Ocular Responses In the absence of oculocephalic responses, it may be necessary to apply more intense and long-lasting vestibular stimulation by irrigating each external auditory canal with up to 50 mL of ice water with the head 30 degrees above the horizontal plane (Chapter 2). An intact response in an unconscious patient consists of tonic responses with conjugate deviation toward the irrigated ear. Tendon Reflexes these reflexes are recorded for the best limb as normal, increased, asymmetric, or absent; minimal responses are best regarded as normal. Asymmetric tendon reflexes should be described, as these may be a clue to lateralized brain or spinal cord injury. Skeletal Muscle Tone this should be recorded as normal, paratonic (diffuse resistance throughout the range of passive motion), flexor (spasticity), extensor (rigidity), or flaccid. But, for the many patients who have nonfocal exams at this point (as described in Chapter 2), it is important to perform basic diagnostic testing. Hypoglycemia or Hyperglycemia the brain depends not only on oxygen and blood flow, but also on the obligate use of glucose for energy (see Chapter 5). Both hypoglycemia and hyperglycemia have deleterious effects on the brain (see Chapter 5). This is often done empirically along with thiamine and naloxone by paramedics, before the patient arrives at the hospital; if not, glucose and thiamine should be given after reaching the hospital. Exact recommendations vary but 50 mL of a 50% intravenous solution of glucose is frequently used.

Other patients with chronic illnesses have suffered ototoxicity from a variety of drugs medicine names discount eldepryl 5 mg on line, including antibiotics such as gentamicin symptoms 9 days past iui buy 5 mg eldepryl mastercard. Finally 3 medications that affect urinary elimination purchase eldepryl with paypal, a variety of drugs medicine 75 yellow 5 mg eldepryl free shipping, including sedatives symptoms for pregnancy cheap eldepryl 5 mg buy online, anticholinergics, anticonvulsants, chemotherapeutic agents, and tricyclic antidepressants, may suppress vestibular and/or oculomotor function to the point where oculo-vestibular reflexes disappear. Pitfalls in the diagnosis of apnea in comatose patients maintained on respirators were discussed earlier. Neuromuscular blockers are often used early in the course of artificial respiration when the patient is resisting the respirator; if suspected brain death subsequently occurs, there may still be enough circulating neuromuscular blocking agent to produce absence of motor function when the examination is carried out. If neuromuscular blockade has been recently withdrawn, guidelines require that a peripheral nerve stimulator be used to demonstrate transmission. Therapeutic overdoses of sedative drugs to treat anoxia or seizures likewise may abolish reflexes and motor responses to noxious stimuli. At least two reports document formal brain death examinations in reversible intoxications with tricyclic antidepressant and barbiturate agents. However, most mistakes in making the diagnosis of brain death are made by inexperienced practitioners, and the training and toolkits have been developed that hopefully will minimize this deficiency. In the past several years controversy has surrounded a small number of cases of brain death leading to public confusion and unwarranted concern about the conceptual integrity of the entity55­57. Patients approximating the features of brain death but not fulfilling the full criteria are in a prolonged coma. Deviations from the complete fulfillment of the clinical criteria for brain death thus create an unknown but finite risk that other abnormalities on the clinical exam may not reflect irreversible damage. The 2010 update also concluded that alternatives to apnea testing be evaluated and that protocols and examiners be subject to auditing procedures to improve the universality of implementation of brain death assessments. Ultimately, expert reviewers have concluded that accurate application of the clinical brain death examination techniques have not resulted in late recovery in any verified instance (see Fins Chapter 11 for additional discussion). Management of the Brain Dead Patient Major physiologic changes occur as patients transition to brain death, and these require aggressive critical care measures for those patients who are potential organ donors (Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement, 2015). While neuroendocrine function may be preserved in some brain dead patients, supplementation of pituitary axes hormones is frequently practiced. Adequate end organ perfusion frequently requires fluid administration and vasopressors support. Additional medications such as antibiotics are frequently given to optimize organ conditions prior to transplantation. Diagnostic tests such as cultures, bronchoscopy, cardiac catheterization, liver biopsy, and other tests may be required to risk-stratify organs for transplantation. Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. Evidencebased guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Decision making in perceived devastating brain injury: a call to explore theimpact of cognitive biases. The unilateral extension-pronation reflex of the upper limb as an indication of brain death. Apnea test for brain death determination in a patient on extracorporeal membrane oxygenation. Prolonged hemodynamic maintenance by the combined administration of vasopressin and epinephrine in brain death: a clinical study. Unexpected return of spontaneous circulation after cessation of resuscitation (Lazarus phenomenon). Assessment: transcranial Doppler ultrasonography: report ofthe Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Time dependent validity in the diagnosis of brain death using transcranial Doppler sonography. Radionuclide studies in the determination of brain death: criteria, concepts, and controversies. Chapter 11 Disorders of Consciousness in Clinical Practice Ethical, Legal and Policy Considerations Joseph J. It especially critical that surrogates understand that the probability of the recovery of consciousness is dynamic and depends upon anatomic locale, etiology, and duration. Because of the rudimentary nature of this emerging nosology, it is inevitable that patients with variable injuries and outcomes will be included in diagnostic categories that are too broad and heterogeneous. This can make prognostication difficult and complicate efforts to achieve greater diagnostic clarity. When speaking with surrogates, a delicate balance needs to be achieved between too quickly foreclosing any prospect of recovery and the offering of false hope. To mitigate these challenges clinicians must assume a fiduciary obligation on behalf of patients entrusted to their care. The physician must ensure that the patient has received the appropriate evaluation and requisite amount of clinical care-diagnostic, therapeutic, and rehabilitative-that would allow for informed decisions by surrogates about treatment decisions. At times this will mean respecting decisions to forgo lifesustaining therapies when surrogates believe that ongoing treatment would be burdensome and result in an existence that would have been unacceptable to the patient or inconsistent with his or her prior wishes. And even as they help patients work toward recovery, they must accept that this pursuit may entail disproportionate burdens. This creates a complex ethos of care which must at once must affirm a right to care and yet preserve a right to die. Just a couple of decades ago, before the advent of more sophisticated imaging data, clinicians would make determinations based on bedside assessment. Opinions were often expressed categorically with value-laden statements like there "was no hope for meaningful recovery. A decade ago, Wijdicks and Rabinstein advised practitioners to lower their expectations for patients in the comatose state. They counseled, "The attending physician of a patient with a devastating neurologic illness will have to come to terms with the futility of care. Those families who are unconvinced should be explicitly told they should have markedly diminished expectations for what intensive care can accomplish and that withdrawal of life support or abstaining from performing 11 Disorders of Consciousness in Clinical Practice 451 complex interventions is more commensurate with the neurologic status. In an unpublished manuscript in his papers, he wrote: We have studied over a 100 patients. This leaves a middle group for whom more information is needed but where presenting every effort at treatment must be made to know their maximal potential and how to judge their early signs. The dynamic quality of these brain states is further complicated by the fact that the clinical neurology of disorders of consciousness is undergoing a profound transition from behavioral assessment, done classically at the bedside, to a more mechanistic and circuit-based approach utilizing neuroimaging and electrophysiological data. The challenge is that, in some circumstances, there may be a discordance between what is observed in the bedside exam and what may be occurring within the brain when assessed by other measures. While diagnostic criteria have traditionally been governed by observable clinical data, this approach is becoming increasingly less tenable, creating uncertainty as to whether to rely on historical clinical methods or to utilize neuroimaging or electrophysiologic metrics, which remain investigational. This remains a critical distinction because patients who are minimally conscious are conscious, whereas vegetative state patients, with whom they are confused and classically conflated, are not. There are profound ethical consequences for patient care and well-being when any of these patients are misdiagnosed due to either episodic or a paucity of behavioral or motor signs. Of course, we cannot always know when and if a patient has covert consciousness because their behaviors may be intermittent and our methods remain imprecise. While psychiatry has emphasized descriptive and epidemiological classifications found in the Diagnostic and Statistical Manual of Nervous Disorders, Insel maintains that it needs to evolve to a more circuit-based approach to describe psychiatric conditions,18 as exemplified by emerging neuroimaging data describing the phenomenology of depression and its subtypes. While this transition will cause confusion in the short term, a more precise understanding of these brain states will inevitably lead to more accurate assessment and improved therapeutics. As the great physician William Osler observed in Aequanimitas, "The determination of structure with a view to the discovery of function has been the foundation of progress. While coma is often erroneously conflated with the brain states that follow in common parlance-and sometimes in careless medical practice-it is important to communicate with surrogates that coma is self-limited and is pluripotential in its outcome, depending on its etiology. This range of prognostic outcomes is important to convey as surrogates may assume that this initial loss of consciousness is permanent and make precipitate judgments in light of this misinformation. Brain Death Brain death is defined as irreversible cessation of function of the whole brain including brainstem and higher brain functions. Patients who have sustained prolonged cerebral anoxia or ischemia or have sustained severe traumatic injury or cerebral edema are at risk of brain death, as reviewed in Chapter 10. While brain death remains a viable clinical construct (see Chapter 10), methods for identifying it at the bedside remain controversial. Brain death, as a clinical entity, was first proposed in 1968 by an Ad Hoc Committee at the Harvard Medical School. Their 11 Disorders of Consciousness in Clinical Practice 453 deliberations followed the first cardiac transplant by Dr. Beecher advanced the radical proposition that organs be retrieved from the "hopelessly comatose" patient. That definition advanced the notion that death can be legally defined as the irreversible cessation of whole brain function independent of either a cardiac arrest or cessation of pulmonary function. However, the achievement of this utilitarian greater good at the expense of individual beliefs has not been without some contention. Although generally accepted in professional circles,29 the concept of brain death is not well understood among lay people when consent for organ donation is sought. After "proclaiming" the patient dead, the patient demonstrated a classic spinally mediated response, or what has been described as a Lazarus reflex, in which the arms rise and the hands come together at the midline as if to pray. The experience, despite his grounding in science was counterintuitive and emotionally disturbing. A more challenging issue is that some segments of our society reject this definition of death, most notably members of some orthodox religious groups33 and others with cultural roots in Asia, most notably Japan, which has only recently legalized brain death determinations. First, it is critical to determine if an objection to brain death is an idiosyncratic grief reaction or truly founded on a theological objection. Even within the Orthodox Jewish tradition, there are subsects that accept brain death and others that do not. Second, if a tradition rejects brain death, it is helpful to cast care decisions within religious law. For example, in Orthodox Judaism there is a mandate to preserve life as well as not prolong the dying process once the patient has been deemed a Goses or one who is imminently dying. This tension can be helpfully discussed with families as they consider right courses of action consistent with their beliefs. These discussions can be guided with an appeal to rabbinic authorities who can often provide assistance and comfort families. These conversations have become more complicated given high-profile cases, such as that of Jahi McMath, in which a brain death diagnosis has been disputed. Absence of brainstem reflexes may be due to inadequate exclusion of historical confounders like sedative agents or hypothermia. Practically there could be inadequate adherence to established guidelines set out by the American Academy of Neurology39,40 at either the institutional policy level41 (although data indicate improving uniformity)42 or through the practices of individual practitioners who either fail to conform to national guidelines or their local hospital policies. Ancillary testing may help validate or confirm diagnostic assessment (see Chapter 10) in the setting of religious or moral objections to brain death, but this approach is not without the risk of false-negative data. To increase support for brain death in Israel among Orthodox Jews who might be opposed, the Israeli Brain Death Act was modified in 2009 to include mandatory use of ancillary tests in addition to bedside evaluation, which included apnea testing. While these scholars admit that there might be public policy reasons to view these patients as legally dead, they are in fact "biologically alive but psychologically dead. Many commentators viewing brain death biologically point to the necessity of an integrative homeostatic function for life and the lack of this function in brain death versus the vegetative state. In brain death, the minimal autonomic control provided by the brainstem seen in the vegetative state is absent even as higher cortical integrative function is absent in the vegetative state. While he does not believe that cases like McMath "present a fundamental challenge to the diagnosis of death by neurological criteria," he does urge additional clarification about how the bright line distinctions of the law can incorporate the continuity of biological processes. As Jennett and Plum classically described it, patients are in a state of wakeful unresponsiveness in which the eyes are open but there is no awareness of self, others, or environment. If eyes are the metaphorical window to the soul, it can be disheartening for families to learn that the opening of the eyes of a loved one in the vegetative state as they emerge from coma are unseeing and unknowing. Quinlan spoke of the tragic moment when she realized that her daughter, Karen, was unaware even as her brainstem recovered and her eyes opened. They need to appreciate that these are autonomic behaviors, much like breathing and the maintenance of a heartbeat, controlled by brainstem activity. Explicating this distinction is important when the patient first enters the vegetative state, lest these behaviors be understood as evidence of awareness or consciousness. This is a point even lost on clinicians who may erroneously believe, or may have been taught, that the persistent vegetative state is invariably permanent. The sequence of recovery that may occur-and its probabilistic likelihood depending on known etiology- should be shared with surrogates. This can be tremendously helpful to them because it prepares them for what the future might hold and milestones that require due attention. Insight into these markers is especially empowering to surrogates once the patient has left the acute care setting and the standards of assessment are more variable. This is a critical backdrop for discussions at the bedside, and it is important for clinicians to understand that the vegetative state has an outsized place in the history of bioethics and the evolution of the right to die. Since the late 1960s, bioethics has been predicated on the evolution of selfdetermination and autonomy. The right to die was established in American jurisprudence through cases involving patients in the vegetative state. Plum that the brain works in essentially two ways, the vegetative and the sapient. Nothing could or should be done because once the permanent vegetative state was reached it was immutable. This logic and public endorsement of an autonomy ethic held in two other cases involving individuals in the vegetative state: Nancy Beth Cruzan62 and Terri Schiavo. The Court ruled that patients have a right to refuse life-sustaining therapy, including the right to refuse artificial nutrition and hydration.

Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus 47 medicine quinine purchase eldepryl online from canada. Treatment of refractory status epilepticus with pentobarbital treatment tinnitus 5 mg eldepryl buy mastercard, propofol treatment bulging disc buy cheapest eldepryl, or midazolam: a systematic review medications that cause constipation 5 mg eldepryl purchase amex. Is pentobarbital safe and efficacious in the treatment of superrefractory status epilepticus: a cohort study medications covered by medicaid generic eldepryl 5 mg visa. The effect of mild hyperthermia and hypothermia on brain damage following 5, 10, and 15 minutes of forebrain ischemia. Eye care for patients receiving neuromuscular blocking agents or propofol during mechanical ventilation. A randomised controlled study of the efficacy of hypromellose and Lacri-Lube combination versus polyethylene/Cling wrap to prevent corneal epithelial breakdown in the semiconscious intensive care patient. The purpose of this generalizable strategy is to stabilize the patient and prevent further brain injury while determining the specific cause of impairment of consciousness. Once the specific cause is identified, though, attention turns to dealing with the set of problems inherent to the underlying disorder. As treatment in psychogenic coma is mostly supportive, we will refer to Chapter 6 for the management of this topic. The focus of each of these sections will be on a discussion of the primary treatment of the cause for impaired consciousness as well 8 Management of Frequently Encountered Causes of Unconsciousness 327 as the management of frequently encountered complications, with particular attention to therapies aimed at primary and secondary processes that impair consciousness. For certain diagnoses such as trauma and ischemic stroke, systematic management protocols with clearly defined algorithms guide efforts of dedicated multidisciplinary management teams. Once initial imaging has ruled out a destructive or compressive lesion, other tests may be obtained to rule out nonstructural pathologies and infratentorial structural mass lesions (see Chapter 7). In equivocal cases, lumbar puncture can be done to make the diagnosis (for details, please refer to Chapter 4). The initial impression and concern is formed based on history and clinical examination. The most important laboratory test that allows narrowing down the differential diagnosis and guiding emergency management is an imaging study. If the patient is suspected from history and exam to be suffering from a supra- or infratentorial mass lesion, it is important to determine how severe the symptoms are and estimate how rapidly they are worsening as it may be necessary to intervene and stabilize the patient before the scan. Assess cardiopulmonary stability: may need central line placement, cardiopulmonary resuscitation b. Antifibrinolytic therapy: aminocaproic acid 4 g bolus followed by 1 g/hr infusion (caution if active myocardial infarction, history of any stents or revascularization procedure, stop 4 hours before angiography). Seizures: load with fosphenytoin 20 mg/kg and maintained on 100 mg three times a day until the aneurysm is treated (phenytoin or levetiracetam are alternatives). Arterial line and central line placement for all poor-grade patients, consider for all c. Multimodality monitoring: in some comatose patients may consider invasive monitoring of the brain tissue: intracranial pressure, brain tissue oxygenation, regional cerebral blood flow, microdialysis, jugular bulb oxygenation saturation, electrical activity Management of medical complications a. Tight blood pressure control, use as needed continuous infusions of vasopressors (phenylephrine or norepinephrine) and anti-hypertensives (nicardipine, labetalol, dobutamine, milrinone) c. Fever: achieve normothermia with Tylenol, cooling blankets, cooling pads, intravascular cooling, perform aggressive shivering control d. Glucose: insulin sliding scale or continuous infusion to keep serum glucose < 200 mg/dL, avoid hypoglycemia f. If possible, intubation should be avoided as this will limit the neurological examination but the risk of aspiration pneumonia and rebleeding from elevated blood pressure need to be taken into account. These threats to vital function need to be addressed first regardless of the underlying etiology (for details, please refer to Chapter 7). Prognostication of long-term outcomes is challenging and clinical scales5 are available but should be used with caution. Patients with poor clinical grade, large amounts of subarachnoid and intraventricular blood, large aneurysms, or those with external cerebrospinal fluid-drainage are at highest risk of early rebleeding. Tylenol as well as opiates with less sedative and hypotensive potential, such as fentanyl, are preferred. Elective procedures that may lead to agitation such as nasogastric tube placement should be deferred, and unstable patients undergoing unavoidable procedures such as arterial line or central line placement should be adequately premedicated. Systolic blood pressure should be lowered typically below 140 or 160 mm Hg9 using intravenous boluses of labetalol (alternatives include hydralazine or continuous infusions of labetalol or nicardipine). The possibility of an underlying coagulopathy should be assessed based on the history, presentation, and emergency laboratory tests and, if it is found, should be addressed promptly. This must be followed immediately with fresh frozen plasma, approximately 2 units every 4 hours, and vitamin K, until the clotting defect is reversed. These patients typically have depressed arousal (Hunt and Hess grades 4 and 5) but, after placement of ventricular drainage catheters, they may show significant and rapid improvement of consciousness. More advanced mechanical, magnetic, and ultrasound guiding systems are available, but because they add to the technical difficulty of the procedure, they may increase the time to successful placement and have therefore not yet been universally accepted. Guidelines9,18 do not recommend prolonged seizure prophylaxis, but practice varies widely. It is common to provide seizure prophylaxis during the perioperative period, especially in poor-grade patients or those with mass effect, but some continue the coverage throughout the intensive care unit stay. The decision whether to treat the aneurysm definitively with coil embolization or neurosurgical clipping is generally made during the initial angiography. The choice of treatment depends on a variety of factors, including age, size and location of the aneurysm, and, perhaps most importantly, the expertise that is immediately available. However, the most important criterion is that the bleeding source should be secured as quickly as possible, preferably within 24 hours of hemorrhage. This reduces cerebral blood flow, leading to loss of consciousness and at times to watershed infarcts. These surgery-related changes appear as infarcts adjacent to the surgical site that do not respect vascular territories. Modern minimally invasive surgical techniques have made these infarcts rare and treatment is nonspecific. Preventing such infarcts is best managed by measures that treat the herniation syndrome (see Chapter 7). This complication, which may represent more diffuse vasospasm and prolonged inadequate cerebral blood flow, is associated with poor functional outcome, cognitive impairment, and decreased quality of life (for details on pathophysiology and diagnosis, please refer to Chapter 4). Management starts with preventive strategies that all patients should receive, including 60 mg of oral nimodipine every 4 hours for the first 21 days after hemorrhage (in Europe, intravenous nimodipine is also available), with dose adjustments and safety margins for hypotension (see Table 8. The combination of hypertension, hypervolemia, and hemodilution, termed triple-H therapy, has been propagated for years with modest results in small trials and meta-analyses. Isotonic fluids such as normal saline are recommended, and dextrose and free water in the intravenous fluids should be avoided. Interventional neuroradiological approaches to dilate narrowed cerebral vessels in vasospasm include balloon angioplasty and intraarterial administration of calcium channel blockers, currently most frequently verapamil or nicardipine. These interventions are of uncertain benefit as angioplasty risks vessel rupture and provides only transient relief; if successful, it may shunt blood from areas that remain underperfused, thus worsening the ischemia elsewhere. On an experimental basis, administration of calcium channel blockers into the ventricular system and systemic administration of dantrolene have been reported. A number of interventions were not beneficial in clinical trials, including the use of magnesium,38 statins,39 the non-glucocorticoid aminosteroid Tirilazad,40 and intra-arterial administration of papaverine. Management depends on the underlying cause and may involve supporting cardiac function or careful fluid management, balancing the risk of ischemia that requires liberal fluid management against difficulties in oxygenation that demand restrictive fluid management. Prolonged mechanical ventilation is required particularly for those with stupor or coma, and many will need tracheostomy. Timing of tracheostomy is controversial, with some advocating for early tracheostomy. Aggressive pulmonary toilet and frequent suctioning are employed as part of intensive care measures. Antibiotics may be needed but should be given thoughtfully as they are frequently overused. Patients with acute brain injury may hyperventilate,47 leading to hypocarbia with the potential for brain tissue hypoxia. This tight control requires central line and arterial line placement, as well as the administration of vasopressors or antihypertensive medications. Continuous drips are preferred, as these allow more rapid up- or down-titration in patients with quickly changing requirements. Frequently used vasopressors include phenylephrine or norepinephrine, but positive inotropic support (dobutamine, milrinone) may be required depending on the cause of hypotension. Patients in shock may, on a case-by-case basis, benefit from transient intra-aortic balloon pump support. Heart failure is often due to stunned myocardium, which is thought to be due to high levels of circulating catecholamines causing subendocardial ischemia with contraction band necrosis. Echocardiography may identify takotsubo cardiomyopathy, in which there is left ventricular failure and diastolic dysfunction with apical and mid-ventricular akinesis. Transient, severe hemodynamic instability may be seen, and aggressive critical care support is required. Management is challenging as a catecholamine surge is thought to be at least partially causative for the developing cardiomyopathy. Treatment with betablockers is recommended, but this approach is often limited by hypotension. Transient pressure support using inotropic medications is frequently attempted for hypotensive patients with takotsubo pathology,49 but, if unsuccessful, intra-aortic balloon pump counterpulsation may be required. Prevention of venous thrombosis requires prophylaxis with low-dose heparin despite the risk of repeat aneurysmal bleeding. In patients treated with antifibrinolytic therapy prior to aneurysm treatment, thrombotic events including myocardial infarction may complicate the course. Current guidelines recommend blood transfusions to keep the hemoglobin above 8 g/dL. Infratentorial hemorrhages can rapidly progress from presenting with ataxia to stupor and coma when compressing the brainstem and are a surgical emergency. Similarly, patients with supratentorial hemorrhages located close to the ventricles may initially exhibit hemiparesis, and, when the hemorrhage breaks into the ventricle, this may be followed rapidly by impaired consciousness requiring emergent placement of external ventricular drainage. These scores help give an estimate of the predicted short-term mortality and functional outcome, respectively. In addition to older age, larger volume and location of parenchymal blood (infratentorial worse than deep, worse than lobar location), the presence of intraventricular blood, a poor neurological baseline (presence of cognitive impairment), and current neurological exam (coma as defined by Glasgow Coma Score of 8 or lower) factor into these scores. Guidelines recommend lowering the systolic blood pressure to 140 mm Hg or lower with intravenous administration of a calcium channel blocker. Underlying coagulopathies may include taking oral anticoagulant drugs or antiplatelet medications, and those with inherited or acquired coagulation factor or platelet abnormalities need to be corrected emergently. Patients with known coagulation factor or platelet disorders are managed by replacement of factors and platelets in consultation with the primary hematologist. Rising numbers of patients are treated with oral anticoagulant drugs such as the vitamin K antagonist warfarin and, increasingly, the novel oral anticoagulants that inhibit thrombin or factor Xa. Fresh frozen plasma (2 units, or 500 mL) takes about an hour to thaw and transport and even longer to infuse, especially in older patients who risk congestive heart failure with the fluid load. All patients on vitamin K antagonists should also be given 5­10 mg of intravenous vitamin K slowly (onset of action is at 2 hours, but it may take several days to completely reverse the deficit; therefore, while it should be given immediately, it plays little role in the emergent reversal of anticoagulation). A specific monoclonal antibody to reverse the activity of dabigatran (idarucizumab)11 has recently been introduced, and agents to reverse factor Xa inhibitors. The practitioner needs to weigh the rebleeding risk against the risk of complications due to interruption of anticoagulants and antiplatelet agents. The initial assessment should be directed toward identifying any underlying vascular lesion as this may need to be addressed emergently to prevent rebleeding. Early angiography is required to determine whether an aneurysm is present as these may occasionally present with intraparenchymal hematomas and require treatment by coiling or surgery within the first 24 hours. These have a substantial but lower risk of early rebleeding unless associated with an aneurysm and so typically are treated in a subacute fashion. In addition to the mass effect from the hemorrhage itself, patients may also develop brain swelling. Depending on the location of the hemorrhage, this increasing mass effect will compress local neural or vascular structures and may cause herniation syndromes (Chapter 3). This increasing mass effect is most prominent within the first 72 hours but may persist into the second week. Depending on the location of the bleed, emergent evaluation is required to determine the benefits from early surgical interventions as delayed surgical treatments often are less effective. Such patients require emergency ventricle shunting and may benefit from suboccipital craniotomy if the hematoma exceeds 3 cm in diameter. Brainstem hemorrhages are typically not felt to benefit from surgical interventions. This is frequently associated with severely depressed consciousness, often with coma. Thrombolytic therapy administered via ventricular drainage catheters for those with large third and fourth ventricular hemorrhage80 and catheters placed in large parenchymal hemorrhages may be additional surgical interventions. Serum osmolar gap and sodium should be followed closely if repeat doses are required. Current guidelines recommend treatment of diagnosed seizures, although in cases with large cortical bleeds in which herniation threatens, clinicians may treat prophylactically with antiepileptic medication. The first two patients remained comatose with myoclonus being observed in the second case. The third case recovered consciousness and was discharged to an acute inpatient rehabilitation program. Case-bycase multidisciplinary discussion of the risks and benefits of restarting the anticoagulants is often required.

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References

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