Richa Agarwal, MD

• Instructor in the Department of Medicine

https://medicine.duke.edu/faculty/richa-agarwal-md

To be most effective symptoms nerve damage buy kemadrin online pills, it must be an action that allows dynamic changes in pitch [108] treatment viral meningitis order kemadrin online pills. Markham [109] and Brown [110] agree that the standing position alters muscle tone through the vestibular system symptoms shingles order kemadrin 5 mg without a prescription, being an important source of excitatory influence to the extensor muscles medications you can buy in mexico discount kemadrin 5 mg. All possible strategies to prevent the onset or complications of deficits in joint mobility and muscle performance should be guided by clinical reasoning-oriented and achievement of patient function and independence treatment yellow tongue buy kemadrin online now. Mobility is the coupling of the nervous system with mechanical systems that determine the quality and range of motion of the musculoskeletal system treatment goals order kemadrin 5mg amex. The nervous system, like other somatic structures (muscles, tendons, capsules, etc. Orthopedic manual physical therapy has developed and extended the practice of elongation of the nervous system and various treatment techniques for mobilizing nerve tissue and its adjacent structures. This fact is used as a tool for the diagnosis and treatment of many orthopedic problems. Butler [112] stated that the clinical consequences of an altered biomechanics of the nervous system are recognized and that many disorders attributed to musculoskeletal sources originate or have a significant component in an adverse natural tension. The connection between movement of the nervous system and symptoms demonstrated in orthopedic patients can be explained by the fact that the nervous system may suffer physical injury that jeopardizes neural and connective tissues. The nerve is usually in contact with various tissues, called neural containers or mechanical interfaces adjacent to tissue. Pathological phenomena include bleeding, swelling or scar tissue, or splints and perhaps hypertonic and stiff muscles. The injury may be in the blood supply to the nerve, the nerve itself or the axoplasmic flow (axonal transport). The nervous system consumes 20% of the oxygen present in the arterial circulation, which is necessary for impulse conduction [113]. An increase of 8% in the normal length of a nerve reduces blood flow, and an increase of 15% will result in the complete occlusion of blood flow [114]. Blood vessels in the spinal cord and peripheral nerves have a length and extra-anatomical organization, responsible for movement and normal blood flow [115]. According to Butler [112], alteration of nerve function begins at pressures of 30-40 mmHg. In a healthy person, the pressure in the carpal tunnel with the wrist joint in neutral position reaches 30 mmHg and 100 mmHg with the wrist in flexion, which suggests that a person with hemiplegic flexor spasticity in the wrist joint will have abnormal pressure on the median nerve. The symptoms often seen in the hemiplegic hand may arise, besides other causes, from impaired axonal transport. It is possible that some of the physiological changes seen in the hemiplegic person are due to spasticity (mechanical interface) that influences the axonal flow. The axoplasm displays thixotropic properties, meaning that it flows better when kept in motion [116]. The neural mobilization technique involves movements not only in joints and muscles but also in the nervous system. Following surgery, the physiotherapist should include: movement of the distal parts in all movements made during treatment, mobilization of the nerve itself and trunk motion, strengthening movement of the nervous system and influencing the sympathetic chain. When studying patients with hemiplegia, spinal cord injury or cerebral palsy, it is often observed that the range of motion of a body part is altered by the passive movement of another distant part of the original motion [117]. According to Davies [118], clinical experience shows that there is a loss of movement of neuraxial and peripheral nerves after head injury. This loss results in abnormal postures, increased resistance to movement and loss of selective movements of the trunk and extremities. Currently, there are no scientific studies or evidence of the effect of neural mobilization in the treatment of patients in intensive care. Knowledge in these patients is insufficient to explain the physiological effect of treatment; however, considering the proposals of the technique, neural mobilization could be used with caution in patients in the acute neurological phase, as long as the neurological changes are stable, the patient is conscious, and no acute disease process is present. Under constant re-evaluation, passive mobilization of the nervous system may be appropriate in selected patients. Given this situation, research has attempted to determine the factors that affect the clinical course and several therapeutic modalities have been suggested and implemented in some segments of rehabilitation. Early identification of secondary brain injury is essential for patients because it can be prevented or minimized with appropriate therapeutic management, thus reducing its influence on the ultimate prognosis of the individual. The physical sequelae are proportional to the area affected and the degree of injury, and include paresis/plegia, the deficits following cranial nerve injury, posttraumatic epilepsy and headache, as well as combinations of cerebellar and pyramidal signs and asymmetric pyramidal signs and bilateral extrapyramidal signs. Cognitive sequelae include changes in memory, especially with regard to pre- and posttrauma conditions, as well as difficulties in maintaining attention and concentration [122]. The medical sequelae include those resulting from metabolic, neuroendocrine, cardiovascular, gastrointestinal, respiratory and blood disorders. Hence, the social and economic burdens are carried by the patients and their families. Added to these burdens, patients often have symptoms that may persist for weeks or months after injury, such as headache, dizziness and incoordination, even in the absence of physical deficits [126]. According to the type and degree of involvement, these lesions can be post-trauma prognostic indicators [127-129]. Age: a factor determining the prognosis; the elderly were found to have the worst prognosis of 122 patients after injury [131,132]. However, outcome after surgery in relation to prognosis remains controversial [144-146]. These changes and their recovery are discussed by Katz and Alexander [122], who report that early diagnosis, age and severity of the trauma are the most influential factors in the recovery of post-traumatic amnesia. Change in behaviour: there are reports that patients may develop behavioural changes after injury [121,147]. Such changes may interfere with social reintegration and are more often identified by family members than by patients. However, these results were only partially consistent with other studies in which such changes interfered with social reintegration [122,123,129,135-137]. The brain is responsible for many higher functions, including cognitive abilities, thinking, behaviour and motor skills. Therefore, the impact of brain injury in the lives of patients and their families can be devastating, whether personal, social, monetary, or a combination thereof. With regard to therapeutic perspectives, much has been invested in management and treatment; however, they incur high costs for public and private health services, not all of which guarantee the multidisciplinary care (medical, nursing, physiotherapy, psychotherapy, occupational therapy, etc. The widespread use of rigorous clinical monitoring, guiding therapeutic interventions in cardiac and neurological functions, allows the therapist to predict the degree of attention patients require not only in mechanical ventilation, but also in the prevention of respiratory and neuromuscular failure. These precautions minimize pulmonary complications, provide early intervention, and contribute to a better prognosis after brain injury. Intracranial pressure monitoring in intensive care: clinical advantages of a computerized system over manual recording. Crit Care 2007; 11: R7 1670 Physiotherapy: An Essential Tool in Neurocritical Care 4. Effect of endotracheal suctioning on cerebral oxygenation in traumatic brain-injured patients. Influence of positive end-expiratory pressure on pressure and cerebral perfusion pressure in patients with acute stroke. Cough in spinal cord injured patients: the relationship between motor level and peak expiratory flow. Spinal Cord 1997; 35: 299-302 1671 Intensive Care in Neurology and Neurosurgery 24. Cough in spinal cord injured patients: comparison of three methods to produce cough. Intravenously administered lidocaine prevents intracranial hypertension during endotracheal suctioning. The effect of preoxygenation technique on arterial blood gases in the mechanically ventilated patient. Intracranial pressure changes in brain-injured patients requiring positive end-expiratory pressure ventilation. Acta Neurochir Suppl 2002; 81: 99-101 1672 Physiotherapy: An Essential Tool in Neurocritical Care 43. Lung recruitment maneuver in patients with cerebral injury: effects on intracranial pressure and cerebral metabolism. Effects of controlled mechanical ventilation on respiratory muscle contractile in rabbits. Respiratory muscle training in patients with moderate to severe myasthenia gravis. The Functional Independence Measure: its use to identify rehabilitation needs in stroke survivors. Using Functional Independence Measure profiles as an index of outcome in the rehabilitation of brain-injured patients. Characteristics of the Functional Independence Measure in traumatic spinal cord injury. Inflammatory markers are associated with ventilator limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Morbidity, mortality, and quality-of-life outcomes of patients requiring or 14 days of mechanical ventilation. Physical therapy utilization in intensive care units: results from a national survey. Mobilizing Patients in the Intensive Care Unit: Improving Neuromuscular Weakness and Physical Function. Early Mobilization of Critically Ill Patients: Reducing Neuromuscular Complications after. Explore the benefits of using a kinetic therapy protocol to improve patient outcomes and lower care costs in critical care units. The impact of continuous lateral rotation therapy in overall clinical and financial outcomes of critically ill patients. Discordance between cardiopulmonary physiology and physical therapy: toward a rational basis for practice. The safety of mobilization and its effect on hemodynamic and respiratory status of intensive care patients. Positioning practices for ventilated intensive care patients: current practice, indications and contraindications. Australian Critical Care 2006: 19: 122-32 1674 Physiotherapy: An Essential Tool in Neurocritical Care 82. Why does prophylaxis with external pneumatic compression for deep vein thrombosis fail Early rehabilitation of higher cortical brain functioning in neurosurgery, humanizing the restoration of human skills after acute brain lesions. Franckeviciute E, Kriscinas A Peculiarities of physical therapy for patients after traumatic brain injury. The importance of stretch and contractile activity in the prevention of connective tissue accumulation in muscle. Contractures in the post-stroke wrist: a pilot study of its time course of development and its association with upper limb recovery. Reduction of hypertonicity by early casting in a comatose head-injured individual. Edinburgh: Churchill Livingstone, 1995 1675 Intensive Care in Neurology and Neurosurgery 102. The use of casts in the management of joint mobility and hypertonia following brain injury in adults: a systematic review. Evaluation of extensibility, passive torque and stretch reflex responses in triceps surae muscles following serial casting to correct spastic equinovarus deformity. Measurement of the flow properties of isolated axoplasm in a defined chemical environment. But the belief that this improved outcome may be due to technological advance alone is not entirely true. Monitoring of intracranial pressure and cerebral oxygenation provides us with more physiological information for making decisions; however, most care measures, rather than modify the results, depend on very simple and common manoeuvres such airway control, prevention of hyperthermia and hypotension, and strict monitoring of blood glucose among others. Growing scientific evidence supports the fact that specialized units with doctors and nurses trained in neurological/surgical intensive care have a great impact and favourable effect on clinical outcomes [1]. The primary insult or injury is the physical damage that occurs at the moment of injury. This injury is already established at the time of admission to hospital and we can do little about it (Table 93. Sometimes the effects associated with secondary injury may have extracerebral origin. Cerebral edema, metabolic disorders, calcium toxicity, cytotoxic injury, inflammation or apopto- Table 93. Episodes of hypotension, hypoxia, hyperglycemia, hypercapnia, for example, double and sometimes triple the morbidity and mortality of patients with neurological injuries, regardless of the type of injury or its initial severity. In general, the initial damage cannot be reversed, whereas secondary injury is often preventable or reversible. In patients with acute brain injury, great care should be focused on avoiding or at least minimizing secondary insults. When analyzing the data objectively, it is clear that the causes of the decline in mortality from trauma in the past 20 years have been the ability to decrease the influence of secondary insults to the injured brain. Much has been written on this aspect and on the importance and prevalence of some actions over others; however, there is consensus among experts that written protocols greatly reduce the probability of error, promote the uniqueness of criteria between care team members, and reduce morbidity and mortality rates. In 2005, Jean Louis Vincent [2] proposed a mnemonic for remembering the most important aspects in the daily care of critically ill patients.

Most factors found to correlate with poor outcome can be directly traced to the degree of disease progression at the time of diagnosis treatment kitty colds order kemadrin 5mg mastercard. The only way to reduce mortality and morbidity is by early diagnosis and timely recognition of complications medications heart disease buy 5 mg kemadrin otc. Aggressive and appropriate care within the intensive care unit setting can minimize associate brain injury and improve the chance of a good outcome medications and mothers milk 2016 buy kemadrin once a day. A prospective study of the risk of tuberculosis among intravenous drung users with human immunodefieciency virus infection medications made from plasma purchase kemadrin us. Central nervous system tuberculosis with the acquired immunodeficiency syndrome and its related complex treatment genital herpes cheap kemadrin 5mg without prescription. Estimating mortality from tuberculous meningitis in a community: use of available epidemiological parmeters in the Indian context medicine 60 buy kemadrin with american express. Comparison of diagnostic criteria of tuberculous meningitis in human immunodeficiency virus-infected and uninfected children. The clinical benefit of adjunctive dexamethasone in tuberculous meningitis is not associated with measurable attenuation of peripheral or local immune responses. Marked increase of matrix metalloproteinase 9 in cerebrospinal fluid of patients with fungal or tuberculous meningoencephalitis. Twenty years of pediatric tuberculous meningitis: a retrospective cohort study in the western cape of South Africa. The clinical, radiological and pathological profile of tuberculous meningitis to patients with and without human immunodeficiency virus infection. Tuberculous encephalopaaaathy with and without meningitis: clinical features and pathological correlations. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features. J Clin Microbiol 2004; 42: 378-9 1047 Intensive Care in Neurology and Neurosurgery 32. Diagnostic accuracy of neucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis. Tuberculosis of the central nervous system: overview of neuroradiological findings. Definitive neuroradiological diagnostic feature of tuberculous meningitis in children. Comparison of conventional bacteriology with nucleic acid amplification (amplified mycobacterium direct tes) for diagnosis of tuberculous meningitis before and after inception of antituberculosis chemotherapy. Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis. Multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis: epidemiology and control. Multidrug-resistant tuberculosis meningitis: clinical problems and concentrations of second-line antituberculous medication. J Biol Chem 2008; 283: 25273-80 1048 Tuberculous Meningitis: the Critical Issues 51. Temperature changes of > or = 1degree C alter functional neurologic outcome and histopathology in canine model of complete cerebral ischemia. Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage. Preceding infection as important risk factor for ischemic brain infarction in young and middle aged patients. The syndrome of inappropriate antidiuretic hormone secretion in tuberculous meningitis. Hyponatremic natriuretic syndrome in tuberculous meningitis: the probable role of arterial natriutetic peptide. Crit Care Clin 2001; 17: 125-38 1049 Intensive Care in Neurology and Neurosurgery 72. Acute hyponatraemia secondary to cerebral salt wasting syndrome in a patient with tuberculous meningitis. Tuberculous meningitis complicated with hydrocephalus and cerebral salt wasting syndrome in a three-year-old boy. Cerebral infarction and cerebral salt wasting syndrome in a patient with tuberculous meningoencephalitis. Acute symptomatic seizures: clinical and etiological spectrum in developing countries. Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Clinical importance of the interaction of phenytoin and isoniazid: a report from the Boston Collaborative Drug Surveillance Program. Continuous monitoring and intervention for cerebral ischemia in tuberculous meningitis. The effect of adjuvant steroid treatment on serial cerebrospinal fluid changes in tuberculous meningitis. Vascular endothelial growth factor and blood-brain barrier distruption in tuberculous meningitis. Shunt surgery for poor grade patients with tuberculous meningitis and hydrocephalus: effect of response to external ventricular drainage and other factors on long-term outcome. Cerebral perfusion pressure in central nervous system infections of infancy and childhood. Acute community-acquired bacterial meningitis in adults admitted to the intensive care unit: clinical manifestations, management and prognostic factors. Cerebral perusion pressure-targeted approach in children with central nervous system infections and raised intracranial pressure: is it feasible Dev Med Child Neurol 1991; 33: 396-405 1051 Intensive Care in Neurology and Neurosurgery 110. Am J rop Med Hyg 1998; 58: 26-34 1052 59 Acinetobacter Infections: An Emerging Problem in the Neurosurgical Intensive Care Unit A. One of the main reasons for the present increased interest in this genus is the emergence of multiresistant strains, several of which are pan-resistant to antibiotics and suddenly cause an outbreak of infection [1]. Multidrug-resistant Acinetobacter baumannii is a rapidly emerging pathogen in the healthcare setting, where it causes infections including bacteraemia, pneumonia, meningitis, urinary tract infections, and wound infections. The crude mortality rate associated with bacteraemia is approximately 52% and that associated with pneumonia ranges from 23 to 73% [2,3]. It is among the most difficult antimicrobial-resistant Gram-negative bacilli to control and treat due to its ability to survive under a wide range of environmental conditions and to persist for extended periods of time on surfaces, making it a frequent cause of outbreaks of infection and an endemic healthcare-associated pathogen. This is an especially severe event in such infections as post-surgical meningitis because the choice of an antibiotic depends not only on the sensitivity of A. Multidrug-resistance complicates the treatment of infection, making the search of new agents imperative and the return to old drugs for optimal treatment of this multidrug-resistant organism. The focus of this review is to summarize the current state of knowledge regarding A. Subsequently, several changes were introduced in to the taxonomic classification of Acinetobacter spp. The genus Acinetobacter initially en1053 Intensive Care in Neurology and Neurosurgery compassed a heterogeneous collection of non-pigmented, oxidase-positive and oxidase-negative Gram-negative rods [3,6-8]. It appears as bacilli during the rapid growth phase and as cocobacilli in the stationary phase [9]. Some strains can survive environmental desiccation for weeks, a characteristic that promotes transmission through fomite contamination in hospitals [13]. In healthcare settings, colonized and infected patients are often the sources of A. Acinetobacter has been isolated from pasteurized milk, frozen foods, chilled poultry, foundry, and hospital air, vaporizer mist, tap water faucets, peritoneal dyalisate baths, bedside urinals, washcloths, door handles, keyboards, angiography catheters, ventilators, contaminated gloves, duodenoscopes, laryngoscope blades, plasma protein fraction, and hospital pillows [14-16]. This ability to grow on medical equipment and throughout the hospital environmental emphasizes the need for special attention to disinfection [17-20]. Up to 25% of healthy ambulatory adults exhibit cutaneous colonization and 7% of adults and children have transient pharyngeal colonization. Differentiating between colonization and infection has clinical and therapeutic relevance because the presence of colonized or infected patients is important in maintaining the organism in the hospital. Acinetobacter baumannii can cause community-acquired infections although less frequently than nosocomial infections. Multidrug-resistant Acinetobacter infection has been reported among patients residing in rehabilitation and long-term care facilities, as well as in acute care hospitals [24-26]. In addition to transmission, the emergence of resistance occurs in the context of selective pressure from broad-spectrum antimicrobial therapy with carbapenems or thirdgeneration cephalosporins. The relative contribution of antimicrobial selective pressure and transmission between patients to the emergence of multidrug-resistant Acinetobacter spp. The most common definitions of multidrug resistance are carbapenem resistance or resistance to more than three classes of antimicrobials [32]. The resistance rate varies between geographic areas, hospitals and even different hospital wards within the same hospital [34]. Some studies [35] found sensitivity rates of imipenem and amikacin of almost 74% in North America and Europe, 60% and 23%, respectively, in Latin America, and 69. In several countries, the rate of resistance to colistin is now 2-3% in relation to previous use, and heteroresistant populations have emerged which can hinder its future use in monotherapy [41]. Although tigecycline once appeared to be a good alternative to conventional treatments, reports have increasingly described the emergence of resistant strains even during treatment with the drug, severely compromising its use in empirical therapy. Another recent study reported resistance rates of 25%, suggesting that the role of antibiotic therapy with these drugs should be carefully evaluated [40]. Several risk factors for the acquisition of multidrug-resistant strains have been identified. These include the previous use of antibiotic treatments, especially carbapenems and third-generation cephalosporins, followed by quinolones, aminoglycosides and metronidazole, and the number of previous antibiotics. The second most common risk 1055 Intensive Care in Neurology and Neurosurgery factor is the use of mechanical ventilation. The most important problem in multidrug-resistant Acinetobacter is its resistance to carbapenems. These enzymes belong to either Ambler Class B (metallo-lactamases) or class D (oxacillinases) [48]. The other group of enzymes (carbapenem-hydrolysing oxacillinases) consists of oxacillinases with intrinsic carbapenemase activity. A third mechanism of carbapenem resistance involves porins, which are outer-membrane proteins that allow antimicrobials, such as beta-lactams, to permeate in to the bacterial cell. Loss or modification of porin proteins has been shown to confer carbapenem resistance and high-level resistance is observed in the presence of both loss of porin function and expression and production of carbapenemases [47,63]. Another mechanism contributing to carbapenem resistance is the overexpression of bacterial efflux 1056 Acinetobacter Infections: An Emerging Problem in the Neurosurgical Intensive Care Unit pumps that decrease the concentration of beta-lactam antibiotics in the periplasmic space [64]. With less beta-lactam entering the periplasmic space, the weak enzymatic activity of betalactamase is amplified. Besides removing beta-lactam antibiotics, efflux pumps can actively expel quinolones, tetracyclines, chloramphenicol, disinfectants, and tigecycline [66,62,47]. Various factors associated with the emergence of strains resistant to carbapenems and sensitive to colistin have been identified, including prior exposure to quinolones and antipseudomonal drugs and the number of antibiotics used previously [65]. These include aminoglycoside O-phosphotransferases, aminoglycoside N-acetyltransferases, and aminoglycoside O-nucleotidyltransferases. They are mediated primarily by plasmids or transposons that can play a role in the spread of resistance. As mentioned above, a second mechanism of resistance to the quinolones is mediated by efflux systems that decrease intracellular drug accumulation [48]. TetA and TetB are specific transposon-mediated efflux pumps; TetB determines the efflux of both tetracycline and minocycline, whereas TetA drives only the efflux of tetracycline. The second mechanism is the ribosomal protection protein, which shields the ribosome from the action of tetracycline. The tet(M) gene encodes this protein, which serves to protect the ribosome from tetracycline, doxycycline, and minocycline [3,46]. Tigecycline is the first antibiotic of a new class called glycylcyclines that may be useful for multidrug-resistant Acinetobacter [71-73]. Tigecycline overcomes the two major mechanisms of resistance to tetracyclines (ribosomal protection and efflux), but tigecycline resistance emerging during therapy has been reported [72]. Probably this mechanism can be upregulated by the previous use of other antibiotics. The mechanism of resistance to colistin likely resides in modifications in the lipopolysaccharide of A. A strong association has been reported between the use of colistin and the development of resistance in clinical isolates of A. However, this microbe has certain features that allow it to increase the virulence of those strains implicated in infections. Studies have investigated the production of such enzymes as butyrate esterase, caprylate esterase, leucine and aryl amidase which may damage tissue lipids and the potentially toxic role of the lipopolysaccharide component of the cell wall and the presence of lipid A. Apart from sharing factors in common with other Gram-negative bacteria, Acinetobacter spp. Furthermore, the hydrophilicity conferred by the presence of capsular polysaccharides, together with other nonspecific adherence factors. Enzymes able to damage tissue lipids are also produced during the infectious stages of colonization. However, the emergence of strains with high resistance to carbapenems, aminoglycosides and fluoroquinolones [35,36,81] poses a challenge to the clinician; therefore, sulbactam, tigecycline and colistin represent the current therapeutic approaches associated with satisfactory efficacy. More than one of these resistance determinants could be present in the same strain, thus conferring it high-level resistance. A recently developed carbapenem is Doripenem, a novel, forthcoming carbapenem that possesses a broad spectrum of activity against Gram-negative bacteria similar to that of meropenem, while retaining the spectrum of imipenem against Gram-positive pathogens [82].

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Preventing complications medicine youkai watch buy kemadrin on line, restoring function and improving the neurological functional status of patients in order to achieve the greatest degree of independence are among the goals of physical therapy in neurointensive care symptoms brain tumor discount kemadrin online master card. Hence 7 medications that can cause incontinence order on line kemadrin, it is not advisable for the therapist to work solely according to a protocol treatment centers near me kemadrin 5mg overnight delivery. This does not mean ignoring treatment protocols; protocols are important for guiding a group of professionals in the conduct of day-to-day treatment medications known to cause miscarriage purchase kemadrin 5mg on-line, avoiding hasty decisions and therapeutic abuse medicine cabinets surface mount purchase kemadrin pills in toronto. On the other hand, neurointensive physiotherapy, treatment and pre-defined goals can ignore the fluctuating clinical conditions commonly described by patients in the acute neurological phase which requires a more refined therapeutic approach. Some studies report that respiratory physiotherapy in critically ill patients can bring about undesirable consequences, such as impaired oxygen transport resulting from the adverse effects on venous return, cardiac output and systemic blood pressure. This, in turn, leads to decreased venous return, and both can impair cardiac filling, resulting in increased intracranial pressure [9,10]. On the other hand, cardiovascular effects are indeed observed in hypovolemic patients, and the possible temporary increase in intracranial pressure is not reflected in brain injury when cerebral autoregulation is preserved. In practice, physiotherapy and motor rehabilitation need to be informed by the monitoring of brain energy metabolism, for example, as tools to guide the intensity, duration and type of interventions that can be applied to the patient at a given moment. There are still few studies in neurointensive physiotherapy that add to scientifically based evidence. This does not diminish the importance of physical therapy or that it is not practiced; instead, clinical trials in this segment are lacking. In general, scientific research investigating the technical resources and the activities of the physical therapist in neurointensive care require more rigorous methodological design. We need measures of the expressive point of view of monitoring neurological status and the sample size, as in any study design, with the aim to improve physiological outcomes and clinical outcomes such as achieving a lower incidence of pneumonia, shorter duration of mechanical ventilation and hospitalization, among others. The clinical picture is often characterized by prolonged hospitalization and mechanical ventilation, frequent need for tracheostomy due to immobility and bed restriction. In this context, the appropriate management and support of physical therapy will include: assessment of dysfunction, monitoring, and neurointensive physiotherapy. Evaluation of gas exchange and the evaluation of pulmonary complica- respiratory mechanisms in neurointensive care. Both may increase the damage to the airway adjacent to primary lesions, the so-called twilight zone of brain injury. During assessment, the physical therapist will observe the chest and monitor radiological changes, which will guide the diagnosis and monitoring of potential lung disorders, besides the need for physical therapy interventions. Parameter Response observed Score In emergency situations, evaluation is performed concurrently with the basic maEye opening Spontaneous eye opening 4 noeuvres recommended for the initial Verbal stimuli 3 treatment of neurological and neurosurgiPainful stimuli 2 cal patients. The team must be integratMissing 1 ed and well-trained in order to preserve Best verbal Oriented 5 life. Also, further Incomprehensible sounds 2 investigation should be performed as Missing 1 soon as possible. Best motor Obeys commands 6 In the neurological workup, the therapist response Locates painful stimuli 5 must be properly trained to assess the folNonspecific withdrawal 4 lowing parameters. This scale has a positive predictive value of 80-90% for assessing prognosis, with 1020% of patients who may have an incorrect prediction of their prognosis [15]. The neurophysiologic responses to verbal, visual, tactile, and proprioceptive stimulation depend on the ascending activating reticular formation and cerebral cortex. At first, the patient may respond to questions coherently or be unable to answer even after being prompted. Some clinical conditions such as hypoxemia and hypercapnia aggravate the state of disorientation and should be rectified immediately once detected. Pupils Pupillary examination will evaluate pupil diameter, symmetry and light reflexes (Table 92. Since some pupil changes can alert to the need for urgent therapeutic intervention, they should be monitored several times a day and during physiotherapy. Complications such as intracranial bleeding and cerebral edema may cause increased intracranial pressure and/or brain herniation, resulting in changes of the pupils, which can vary rapidly from isocoria to anisocoria or mydriasis and non-reactivity of one or both pupils. These changes are suggestive of dysfunction in the deep supratentorial regions of the internal capsule. It may consist of several deficits, such as loss of selective motor control of balance, righting reactions, primitive reflexes and sensitivity, as well as the presence of abnormal muscle tone. Depending on the extent and severity of injury, the patient presents a clinical picture of paralysis with spasticity, hyperreflexia or hyporeflexia (sagging). Therefore, an increased volume in one or more components will be accompanied by a decrease in others. Monitoring brain hemodynamics includes the evaluation of cerebral metabolic and circulatory function. The coupling of these functions depends on the mechanisms of cerebral autoregulation. The conditions that lead to augmented aerobic metabolism increase the production of carbon dioxide, responsible for vasodilation and appropriate increased microcirculatory cerebral blood flow. In contrast, anaerobic metabolism, concomitant with a reduction in carbon dioxide, mediates vasoconstriction and flow reduction. Values above and below normal represent hyper-or low flow in cerebral oxygen consumption, respectively. These notions of brain hemodynamics guide the team in physiotherapy management and clinical or surgical treatment which require the coupling of neurological function, cardiovascular and respiratory diseases. When performed during mechanical ventilation, respiratory therapy helps to adjust ventilation parameters, weaning and extubation. The use of noninvasive mechanical ventilation is increasingly reported in the literature [19]. Respiratory complications are more frequent in neurocritically ill patients: pneumonia, acute respiratory failure, neurogenic pulmonary edema and atelectasis [20]. Under these conditions, physiotherapy techniques use protective strategies of mechanical ventilation to minimize the symptoms and degree of lung injury [21,22]. Respiratory therapy may promote a temporary rise in intrathoracic pressure and consequent reflex in cerebral hemodynamics and intracranial pressure [9]. Therefore, patients should be approached with special care for each of the techniques applied at the time of therapy. Its role is quite varied, depending on location and tradition of service, level of education, training and experience, and especially the patient characteristics. The features and therapeutic techniques in respiratory therapy include the following. Stimulation of Cough Stimulation of cough is a common technique to treat respiratory complications resulting from the accumulation of secretions, especially in patients with cognitive impairment (no response to verbal commands) and those with high spinal cord injury, in whom paralysis of the trunk and abdomen muscles reduces the ability to generate effective cough. In such patients, there is a close relationship between motor level and peak expiratory flow during cough [23]. Jaeger and colleagues [24] studied the efficacy of three methods of cough stimulation in patients with high spinal cord injury. The methods in1646 Physiotherapy: An Essential Tool in Neurocritical Care volved coughing without manual assistance, with assistance from the therapist, and abdominal electrical stimulation. Inducing coughing is undesirable in patients with increased intracranial pressure. It is contraindicated because it leads to an increase in intrathoracic pressure, decreasing venous return, thereby increasing cerebral blood flow. However, when cerebral autoregulation is preserved, intracranial pressure returns to normal levels immediately after the procedure, demonstrating adequate compliance of the nervous system. Under such conditions, cough can be used as a resource during bronchial hygiene therapy. Endotracheal Suction A constant concern in neurological patients is the aspiration of pulmonary secretions because this can negatively affect the cerebrovascular status by increasing intracranial pressure. Therefore, brain damage can ensue not only from the primary trauma but also secondarily to reduced oxygen to the brain as a result of cerebral edema, ischemia and increased intracranial pressure. Tracheal aspiration refers to the effective removal of endotracheal secretions, aseptically through a suction system. Airway access for the procedure can be achieved by two methods or systems: open and closed. It involves disconnecting the patient from mechanical ventilation for the aseptic introduction of a the probe for aspiration. The second system refers to a multi-use probe enclosed in a plastic cover which is connected to an endotracheal tube and ventilator circuit, allowing aspiration without interrupting mechanical ventilation. There is no consensus in the literature on performing this procedure in the presence of impaired cerebral compliance. The aspiration time should not exceed 15 / 2 to prevent hypoxemia; the suction pressure should not exceed 120 mmHg or the suction flow rate 16 l/min to avoid mucosal trauma. Aspiration should be performed only when pulmonary auscultation reveals rales, the mechanical ventilator display indicates increased peak inspiratory, deterioration of oxygenation demonstrated by a drop in oxygen saturation, and when the movement of se1647 Intensive Care in Neurology and Neurosurgery cretions is audible during respiration. The technique should not be performed at regular intervals because the risk of routine aspiration outweigh its benefits [31]. Despite its being a widely used procedure in neurological patients, endotracheal suctioning is associated with complications including, hypoxemia, changes in partial pressure of carbon dioxide, tracheal mucosal injury, increased intracranial pressure, hypertension, bradycardia and arrhythmias. It can also result in damage to the mucosa and mucociliary system, which is usually operator-dependent, the amount of pressure used, and the establishment of this procedure as a routine [32]. Another study suggested that hyperventilation and hyperoxygenation performed before tracheal aspiration can avoid significant changes in cerebral hemodynamics [33]. There is consensus [34,35] that additional oxygen can be administered in ventilated neurological patients during tracheal aspiration procedures. Conventional Manoeuvres Conventional physical therapy manoeuvres include compression, vibration, locking and unlocking chest manoeuvres, postural drainage, tapping and ventilatory patterns. The authors concluded that the manoeuvres did not significantly affect cerebral perfusion pressure. Chest physiotherapy manoeuvres tend to increase intrathoracic pressure by increasing lung volume. Thoracic Manoeuvres Manoeuvres of manual chest physiotherapy (chest compression, locking and unlocking manoeuvres, thoracic breathing pattern, directed or contralateral) for the reversal of alveolar collapse tend to increase intrathoracic pressure by increasing lung volume and warrant caution in these patients. Therefore, in patients with concomitant brain injury and severe respiratory failure there is a conflict in the therapeutic principles that guide ventilatory support. For these reasons, it is of fundamental importance to join the efforts of the multidisciplinary team in therapeutic decision making, taking in to account the risk-benefit ratio for patients where hypoxia is a major risk factor for complications after injury or brain surgery. Despite the many studies, mostly experimental, on alveolar recruitment manoeuvres, few clinical trials have investigated the effects of these manoeuvres in acute respiratory failure in neurological patients. Since the authors noted an improvement in blood oxygenation, they recommended routine use of this manoeuvre. Muscle Training Recent studies have addressed the complications of mechanical ventilation in the short term, such as reducing the mass and contractile properties of respiratory muscles. Also, Hering and colleagues [45], in a study in pigs with oleic acid-induced lung injury, found that mechanical ventilation in 80% of cases reduced blood flow to respiratory muscles in comparison to spontaneous breathing, despite improvement of the oxygenation index. These factors contribute to our understanding that suppression of spontaneous breathing during mechanical ventilation in patients with primary or secondary neuromuscular disorders adversely affects respiratory muscle activity, impairing the removal of ventilatory support. In this case, the muscle training has a key role in the permanent removal of mechanical ventilation [46]. Stiller and Huff [47] reported that training the muscles of the neck and upper chest in ventilator-dependent quadriplegic patients may improve the vital capacity and allow the ventilator to be disconnected for longer periods. The use of abdominal weight and load resistance muscle training in 11 patients with complete cervical lesion showed significant differences in forced vital capacity, maximum voluntary ventilation, and maximal inspiratory pressure. However, there was no difference between the two techniques studied by Derrickson and colleagues [48]. In other neuromuscular disorders, muscle training can also improve strength and endurance, as reported by McCool and Tzelepis [49]. The authors reviewed seven studies on 1649 Intensive Care in Neurology and Neurosurgery muscle training, involving a total of 75 patients whose training regimen included the use of inspiratory resistance load and isocapnic hyperpnoea. The patients with lower neuromuscular disorders showed significant increases in muscle strength and endurance. Patients with more severe disorders were retainers of carbon dioxide, where there was little change in muscle strength or endurance. Besides the effects on the performance of respiratory muscles, muscle training appears to improve lung function and reduce dyspnoea, as in cases of myasthenia gravis and multiple sclerosis [50]. In such patients, we observed a reduction in periods of pulmonary exacerbation, improved exercise tolerance, cough effective, and less need for mechanical ventilation. In addition, the type of tracheal access must be considered because these patients remain under prolonged mechanical ventilation. Some studies comparing very early tracheostomy intubation with mechanical ventilation reported that tracheostomy assists in weaning from mechanical ventilation and decreases the incidence of infections due to easier suctioning the airways, and generates greater degree of comfort, better mobility, communication and power for the patient [18]. Standardization of physiotherapy assessment and intervention in neurological and neurosurgical patients supports decision making in line with the best scientific evidence and available resources. Objective clinical assessment will require reliable and valid scales that are appropriate to what we want to measure, that establish a baseline before starting treatment, and that allow us to record the degree and duration of response to treatment. The goal of rehabilitation is to reduce the level of disability, reaching the maximum of functional independence, participation and integration in social and economic life.

The risk for extracerebral hemorrhages was greater with anticoagulation than with antiplatelet therapy (5 medications side effects prescription drugs order discount kemadrin on-line. However silicium hair treatment purchase kemadrin 5 mg line, further studies are needed to confirm this finding before this approach can be recommended generally symptoms joint pain fatigue buy kemadrin with american express. Despite evidence from the randomized clinical trials discussed above symptoms 0f colon cancer generic kemadrin 5mg amex, anticoagulation continues to be recommended for some specific clinical situations treatment for pneumonia buy kemadrin us. Apparently medicine norco order 5mg kemadrin fast delivery, patients with acute ischemic stroke ipsilateral to a severe stenosis or occlusion of the internal carotid artery could be an exception to the lack of anticoagulation benefit. However, this was a post hoc analysis with a small number of individuals, so the effect of chance cannot be excluded [120]. No convincing evidence supports anticoagulation for patients with stroke due to large artery atherosclerosis. The use of anticoagulation in cerebral venous sinus thrombosis is based on open case series with no controls. Anticoagulation has been used even in the presence of hemorrhagic infarctions typical of this condition. There are, however, some patients at particularly high risk for recurrent embolic events (eg, those with mechanical heart valves or intracardiac thrombi) who were either not included or underrepresented in the acute antithrombotic therapy stroke trials. Although long-term anticoagulation for secondary stroke prevention may be indicated for these patients, the optimal choice of acute antithrombotic therapy is uncertain. Acute anticoagulation could be considered in this setting when the risk of hemorrhagic complications is low (eg, small ischemic burden and no evidence of hemorrhage on imaging). Cardioembolic strokes have poorer prognosis compared to other subtypes of ischemic strokes, such as atherotrombotic and lacunar forms, due to wider 1199 Intensive Care in Neurology and Neurosurgery ischemic damage and major risk of hemorrhagic transformation with the consequence of higher risk of in-hospital, 30-days and 12-months mortality and severe disability [125127]. The choice of drugs aimed to reduce the cardioembolic risk should take in account the risk of bleedings and carefully weighted. They identify categories of patients at different risk of bleeding assigning points to the considered risk factors. Unfortunately many risk factors are at the same time risks for thromboembolic and for bleeding events, making choice difficult. In the two secondary-prevention trials, the benefit of anticoagulation was represented by a lower incidence of any (ischemic or hemorrhagic) recurrent stroke (52 fewer per 1000 over 1-2. Both primary and secondary prevention studies showed a neutral effect of anticoagulation therapy on mortality [134]. In summary, there is no net benefit or harm associated with the early initiation of anticoagulation, but that the risk of symptomatic hemorrhagic transformation is greater with large infarcts. As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. This reduces the thrombogenicity of clots Rapidly absorbed following oral administration with considerable interindividual variations. Hydroxylated metabolites may be further conjugated prior to excretion in to bile and urine. The metabolites are principally excreted in to the urine; and to a lesser extent in to the bile R-warfarin t1/2=37-89 hours; S-warfarin t1/2=21-43 hours 0. Monitor for changes in the therapeutic and adverse effects of warfarin if acetaminophen is initiated, discontinued or dose changed the antiplatelet effects of acetylsalicylic acid may increase the bleed risk associated with warfarin Allopurinol may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin times and therapeutic effects of warfarin if allopurinol is initiated, discontinued or dose changed Aminoglutethimide may decrease the anticoagulant effect of warfarin by increasing its metabolism. Monitor for changes in prothrombin time and therapeutic effects of warfarin if aminoglutethimide is initiated, discontinued or dose changed the antiplatelet effects of aminosalicylic acid may increase the bleed risk associated with warfarin Amiodarone may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if amiodarone is initiated, discontinued or dose changed Amobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if amobarbital is initiated, discontinued or dose changed Amprenavir may increase the anticoagulant effect of warfarin by increasing its serum concentration Aprepitant may decrease the anticoagulant effect of warfarin by decreasing its serum concentration the protease inhibitor, atazanavir, may increase the anticoagulant effect of warfarin Azathioprine may decrease the anticoagulant effect of warfarin Azithromycin may increase the anticoagulant effect of warfarin by increasing its serum concentration the corticosteroid, betamethasone, alters the anticoagulant effect of warfarin Bezafibrate may increase the anticoagulant effect of warfarin. Monitor prothrombin time and therapeutic and adverse effects of warfarin if bezafibrate is initiated, discontinued or dose changed 1203 Half life Clearance Toxicity Drug interactions Acetylsalicylic acid Allopurinol Aminoglutethimide Aminosalicylic Acid Amiodarone Amobarbital Amprenavir Aprepitant Atazanavir Azathioprine Azithromycin Betamethasone Bezafibrate Intensive Care in Neurology and Neurosurgery Bosentan Butabarbital Bosentan may decrease the anticoagulant effect of warfarin by increasing its metabolism Butabarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if butabarbital is initiated, discontinued or dose changed Butalbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if butalbital is initiated, discontinued or dose changed Capecitabine may increase the serum concentration of warfarin by decreasing its metabolism. Monitor for changes in prothrombin time and therapeutic effects of warfarin if capecitabine is initiated or discontinued. Subsequent cycles of capecitabine may increase this effect Carbamazepine may decrease the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if carbamazepine is initiated, discontinued or dose changed the cephalosporin, cefotetan, may increase the anticoagulant effect of warfarin the cephalosporin, cefoxitin, may increase the anticoagulant effect of warfarin the cephalosporin, ceftriaxone, may increase the anticoagulant effect of warfarin Celecoxib may increase the anticoagulant effect of warfarin the bile acid sequestrant, cholestyramine, may decrease the anticoagulant effect of warfarin by decreasing its absorption Cimetidine may increase the serum concentration of warfarin. Increase monitoring for signs and symptoms of bleeding during concomitant therapy Butalbital Capecitabine Carbamazepine Cefotetan Cefoxitin Ceftriaxone Celecoxib Cholestyramine Cimetidine Ciprofloxacin Cisapride Citalopram Clarithromycin Clofibrate Clopidogrel 1204 Antithrombotic Therapy for Secondary Stroke Prevention Colestipol the bile acid sequestrant, colestipol, may decrease the anticoagulant effect of warfarin by decreasing its absorption the antineoplastic agent, cyclophosphamide may alter the anticoagulant effect of warfarin Danazol may increase the serum concentration and anticoagulant effect of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if delavirdine is initiated, discontinued or dose changed the tetracycline, demeclocycline, may increase the anticoagulant effect of warfarin Desogestrol may alter the anticoagulant effect of warfarin. Monitor for changes in coagulation status if desogestrol is initiated, discontinued or dose changed the corticosteroid, dexamethasone, alters the anticoagulant effect of warfarin the thyroid hormone, dextrothyroxine, increase the anticoagulant effect of warfarin the antiplatelet effects of oral diclofenac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy Dicloxacillin may decrease the anticoagulant effect of warfarin the antiplatelet effects of diflunisal may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy Disulfiram may increase the anticoagulant effect of warfarin the tetracycline, doxycycline, may increase the anticoagulant effect of warfarin Drospirenone may alter the anticoagulant effect of warfarin. Monitor for changes in coagulation status if drospirenone is initiated, discontinued or dose changed Increased risk of bleeding the macrolide, erythromycin, may increase the anticoagulant effect of warfarin Ethchlorvynol may decrease the anticoagulant effect of warfarin Ethinyl estradiol may alter the anticoagulant effect of warfarin. Monitor for changes in coagulation status if ethinyl estradiol is initiated, discontinued or dose changed 1205 Cyclophosphamide Danazol Delavirdine Demeclocycline Desogestrel Dexamethasone Dextrothyroxine Diclofenac Dicloxacillin Diflunisal Disulfiram Doxycycline Drospirenone Drotrecogin alfa Erythromycin Ethchlorvynol Ethinyl estradiol Intensive Care in Neurology and Neurosurgery Ethynodiol diacetate Ethynodiol diacetate may alter the anticoagulant effect of warfarin. Monitor for changes in coagulation status if ethynodiol diacetate is initiated, discontinued or dos the antiplatelet effects of etodolac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy Etonogestrel may alter the anticoagulant effect of warfarin. Monitor for changes in coagulation status if etonogestrel is initiated, discontinued or dose changed. Etoricoxib may increase the anticoagulant effect of warfarin Fenofibrate may increase the anticoagulant effect of warfarin. Monitor prothrombin time and therapeutic and adverse effects of warfarin if fenofibrate is initiated, discontinued or dose changed the antiplatelet effects of fenoprofen may increase the bleed risk associated with warfarin. The antiplatelet effect of flurbiprofen may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if flurbiprofen is initiated, discontinued or dose changed Etodolac Etonogestrel Etoricoxib Fenofibrate Fenoprofen Floxuridine Fluconazole Fludrocortisone Fluorouracil Fluoxetine Fluoxymesterone Flurbiprofen 1206 Antithrombotic Therapy for Secondary Stroke Prevention Fluvastatin Fluvoxamine Fosamprenavir Fosphenytoin Gefitinib Gemcitabine Gemfibrozil Ginkgo biloba Ginseng Glutethimide Griseofulvin Hydrocortisone Ibuprofen Imatinib Indinavir Indomethacin Fluvastatin may increase the anticoagulant effect of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if gemfibrozil is initiated, discontinued or dose changed Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided Additive anticoagulant effects increase the risk of bleeding. Concomitant therapy should be avoided Glutethimide may decrease the serum concentration of warfarin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if glutethimide is initiated, discontinued or dose changed. The antiplatelet effect of ibuprofen may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if ibuprofen is initiated, discontinued or dose changed Imatinib may increase the anticoagulant effect of warfarin increasing the risk of bleeding. The antiplatelet effect of indomethacin may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if ketoconazole is initiated, discontinued or dose changed the antiplatelet effects of ketoprofen may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy the antiplatelet effects of ketorolac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy Leflunomide may increase the anticoagulant effect of warfarin Levamisole may increase the anticoagulant effect of warfarin. The quinolone antibiotic, levofloxacin, may increase the anticoagulant effect of warfarin Levonorgestrel may alter the anticoagulant effect of warfarin. Monitor for changes in coagulation status if levonorgestrel is initiated, discontinued or dose changed Levothyroxine may contribute to the anticoagulant effect of warfarin by increasing the metabolism of vitamin K-dependent clotting factors. Monitor for changes in prothrombin time and anticoagulant effects if levothyroxine is initiated, discontinued or dose changed Liothyronine may contribute to the anticoagulant effect of warfarin by increasing the metabolism of vitamin K-dependent clotting factors. Monitor for changes in prothrombin time and anticoagulant effects if liothyronine is initiated, discontinued or dose changed Liotrix may contribute to the anticoagulant effect of warfarin by increasing the metabolism of vitamin K-dependent clotting factors. Monitor for changes in prothrombin time and anticoagulant effects if liotrix is initiated, discontinued or dose changed Lovastatin may increase the anticoagulant effect warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if lovastatin is initiated, discontinued or dose changed Lumiracoxib may increase the anticoagulant effect of warfarin Ketoprofen Ketorolac Leflunomide Levamisole Levofloxacin Levonorgestrel Levothyroxine Liothyronine Liotrix Lovastatin Lumiracoxib 1208 Antithrombotic Therapy for Secondary Stroke Prevention Meclofenamic acid the antiplatelet effects of meclofenamic acid may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy Medroxyprogesterone may alter the anticoagulant effect of warfarin. The antiplatelet effect of mefenamic acid may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if mefenamic acid is initiated, discontinued or dose changed Mefloquine may increase the anticoagulant effect of warfarin the antiplatelet effects of meloxicam may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy Mercaptopurine may decrease the anticoagulant effect of warfarin Mestranol may alter the anticoagulant effect of warfarin. Monitor for changes in coagulation status if mestranol is initiated, discontinued or dose changed Methimazole may decrease the anticoagulant effect of warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if methimazole is initiated, discontinued or dose changed Methohexital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if methohexital is initiated, discontinued or dose changed Metronidazole may increase the serum concentration of warfarin by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if miconazole is initiated, discontinued or dose changed the tetracycline, minocycline, may increase the anticoagulant effect of warfarin 1209 Medroxyprogesterone Mefenamic acid Mefloquine Meloxicam Mercaptopurine Mestranol Methimazole Methohexital Metronidazole Miconazole Minocycline Intensive Care in Neurology and Neurosurgery Mitotane Moxifloxacin Nabumetone Mitotane may decrease the anticoagulant effect of warfarin the quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of warfarin the antiplatelet effects of nabumetone may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy Nafcillin may increase the anticoagulant effect of warfarin increasing the risk of bleeding. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if nafcillin is initiated, discontinued or dose changed the quinolone antibiotic, nalidixic acid, may increase the anticoagulant effect of warfarin Nandrolone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if nandrolone is initiated, discontinued or dose changed Nandrolone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if nandrolone is initiated, discontinued or dose changed the antiplatelet effects of naproxen may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if nicardipine is initiated, discontinued or dose changed Norethindrone may alter the anticoagulant effect of warfarin. Monitor for changes in coagulation status if norethindrone is initiated, discontinued or dose changed the quinolone antibiotic, norfloxacin, may increase the anticoagulant effect of warfarin Norgestimate may alter the anticoagulant effect of warfarin. Monitor for changes in coagulation status if norgestimate is initiated, discontinued or dose changed the quinolone antibiotic, ofloxacin, may increase the anticoagulant effect of warfarin Orlistat may increase the anticoagulant effect of warfarin Nafcillin Nalidixic acid Nandrolone decanoate Nandrolone phenpropionate Naproxen Nelfinavir Nevirapine Nicardipine Norethindrone Norfloxacin Norgestimate Ofloxacin Orlistat 1210 Antithrombotic Therapy for Secondary Stroke Prevention Oxandrolone Oxandrolone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if oxandrolone is initiated, discontinued or dose changed the antiplatelet effects of oxaprozin may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy Oxymetholone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if pentobarbital is initiated, discontinued or dose changed Pentoxifylline may increase the anticoagulant effect of warfarin Phenobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor phenytoin levels, prothrombin time, and therapeutic and adverse effects of both agents during concomitant therapy Phytonadione (vitamin K) may antagonize the anticoagulant effects of warfarin. The antiplatelet effect of piroxicam may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if piroxicam is initiated, discontinued or dose changed the corticosteroid, prednisolone, alters the anticoagulant effect of warfarin 1211 Oxaprozin Oxymetholone Oxyphenbutazone Paroxetine Pentobarbital Pentoxifylline Phenobarbital Phenylbutazone Phenytoin Phytonadione Piroxicam Prednisolone Intensive Care in Neurology and Neurosurgery Prednisone Primidone Propafenone Propoxyphene Propylthiouracil the corticosteroid, prednisone, alters the anticoagulant effect of warfarin the barbiturate, primidone, decreases the anticoagulant effect of warfarin Propafenone may increase the anticoagulant effect of warfarin Propoxyphene may increase the anticoagulant effect of warfarin Propylthiouracil may decrease the anticoagulant effect of warfarin. Rifampin may decrease the anticoagulant effect of warfarin by increasing its metabolism Additive anticoagulant effects increase the risk of bleeding. Concomitant therapy should be avoided the antiplatelet effects of sodium salicylate may increase the bleed risk associated with warfarin Secobarbital may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if sitaxentan is initiated, discontinued or dose changed St. Warfarin should be administered at least 2 hours before or 6 hours after sucralfate administration. Monitor for changes in prothrombin time if sucralfate is initiated, discontinued or dose changed Quinidine Quinine Ranitidine Rifabutin Rifampin S-adenosylmethionine Salicylate-sodium Secobarbital Sitaxentan St. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if sulfadiazine is initiated, discontinued or dose changed Sulfamethoxazole may increase the anticoagulant effect of warfarin by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if sulfisoxazole is initiated, discontinued or dose changed the antiplatelet effects of sulindac may increase the bleed risk associated with warfarin. Concomitant therapy is contraindicated due to significant increase in bleed risk Telithromycin may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if testolactone is initiated, discontinued or dose changed Testosterone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if testosterone is initiated, discontinued or dose changed the androgen, testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, warfarin. Monitor for changes in the therapeutic effect of warfarin if testosterone is initiated, discontinued or dose changed Tetracycline may increase the anticoagulant effect of warfarin Thiopental may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if thiopental is initiated, discontinued or dose changed 1213 Sulfamethoxazole Sulfinpyrazone Sulfisoxazole Sulindac Tamoxifen Telithromycin Tenoxicam Testolactone Testosterone Testosterone Propionate Tetracycline Thiopental Intensive Care in Neurology and Neurosurgery Tiaprofenic acid the antiplatelet effects of tiaprofenic acid may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy Increased bleeding risk. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if tolbutamide is initiated, discontinued or dose changed the antiplatelet effects of tolmetin may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy the androgen, Testosterone, may incrase the anticoagulant effect of the vitamin K antagonist, and warfarin. Monitor for changes in the therapeutic effect of warfarin if testosterone is initiated, discontinued or dose changed the prostacyclin analogue, treprostinil, increases the risk of bleeding when combined with the anticoagulant, Warfarin. A dosage reduction may be required if used in combination the anticoagulant effect of Warfarin, a Vitamin K antagonist, may be altered by antineoplastics such as Trimetrexate.