By U. Taklar. Southwest University. 2019.
It is also well recognized that hospitalized patients who have experienced prolonged starvation have greater problems with wound healing and that diminished protein stores are associated with increased susceptibility to infection discount diclofenac master card. For critically ill obstetric patients buy diclofenac 100mg otc, nutritional support is thought to be important for both maternal and fetal outcomes buy diclofenac 50 mg cheap. As with nonobstetric patients diclofenac 100 mg on-line, enteral nutrition is preferred over parenteral nutrition to avoid the risk of complications associated with central venous catheters, to reduce expense, and to minimize intestinal mucosal atrophy . Pregnancy is associated with decreased lower esophageal sphincter tone and decreased gastric motility; therefore, nasoduodenal tubes are preferred over nasogastric tubes to decrease the likelihood of reflux and aspiration, although scientific evidence for this is lacking. Blood glucose levels should be measured, along with serum electrolyte concentrations, acid–base status, and renal and hepatic function. Periodic nutritional assessment should include evaluation of nitrogen balance, lymphocyte counts, transferrin, maternal weight, and fetal growth by ultrasound. Deficiencies of these vitamins may lead to fetal neural tube defects, eye abnormalities, and intracerebral hemorrhage . Anticoagulation should be instituted immediately in all patients without clear contraindications, such as active bleeding, rather than delaying therapy pending conclusive diagnostic studies. Patients with extremes of weight <50 kg or >90 kg, should be considered for anti-Xa monitoring every 4 to 6 weeks, so that twice-daily regimens achieve anti-Xa levels of 0. A recent review identified 189 pregnant women who received thrombolytics during pregnancy for venous thromboembolism. Tissue plasminogen activator does not cross the placenta, and the risk of allergic reactions is lower than that of streptokinase. If thrombolytic therapy is used during pregnancy, it seems reasonable to limit the duration of therapy to the time needed for restoration of acceptable hemodynamic function and to discontinue therapy at least 4 to 6 hours antepartum. Continuous uterine massage and methylergonovine maleate should be used postpartum if thrombolytic therapy was only recently discontinued. Aminocaproic acid crosses the placenta readily and is teratogenic, so this should not be used when rapid reversal of the lytic state is needed before delivery. Laboratory monitoring of the lytic state during thrombolytic infusion is not recommended, because clot lysis and risk of bleeding do not correlate well with laboratory measurement of the lytic state . If delivery is anticipated in the next 6 hours, initiation of heparin is delayed until after delivery. Thrombolysis is contraindicated during delivery and the immediate postpartum state because of the bleeding risk. There were no maternal deaths, although fetal death was reported in six cases and preterm delivery in four cases . Surgical embolectomy should be reserved as a lifesaving measure for the mother because of the high incidence of fetal loss . Catheter-directed therapy may include catheter-directed mechanical embolectomy and/or catheter-directed thrombolytic therapy. Among four cases using these techniques during pregnancy, one fetal death and one preterm delivery were reported . Once the patient has stabilized, continuous intravenous heparin can be transitioned to subcutaneous therapy. The patient should be anticoagulated for the remainder of the pregnancy and for at least 6 weeks postpartum . The timing of reinstitution of anticoagulation following delivery will vary depending upon the type of delivery, the presence of bleeding, and the presence of a neuraxial anesthesia catheter. As long as significant bleeding has not occurred, anticoagulation with a heparin may be resumed 6 hours after a vaginal birth or 12 hours after a cesarean section. If pulmonary capillary wedge pressures are elevated, it seems reasonable to use a diuretic to reduce hydrostatic pressures across the injured capillary endothelium. In addition to fluid resuscitation to reverse hypotension, vasopressor therapy is frequently required. For active bleeding, transfusion with red blood cells, fresh-frozen plasma, cryoprecipitate, platelets, and factor replacement is indicated. When uterine bleeding is refractory to these interventions, exploration for uterine tears or retained placenta should be considered. Venous Air Embolism the goals of treatment are to identify the source of air entry, prevent further air entrainment, restore circulation, and remove embolized air. Placing the patient in the left lateral decubitus position may restore forward blood flow by causing the bubble of air to migrate away from the right ventricular outflow tract to a nonobstructing position [19,29]. Aspiration of air from the right atrium, right ventricle, or pulmonary outflow tract can be attempted with a central venous or pulmonary artery catheter [19,20]. Air bubble resorption may be accelerated by ventilating the patient with 100% oxygen to facilitate diffusion of nitrogen from the embolus. When air embolism occurs during general anesthesia, nitrous oxide should be discontinued because it has a high solubility and tends to increase the size of air bubbles in the pulmonary vasculature [19,20]. Patients with continued evidence of neurologic deficits or cardiopulmonary compromise because of air embolism should be considered for hyperbaric oxygen therapy. Hyperbaric oxygen accelerates nitrogen resorption, decreases air bubble size, and increases the arterial oxygen content [19,20]. Use of anticoagulation with heparin has been suggested to treat fibrin microemboli, but has not been formally evaluated . Aspiration of Gastric Contents For patients with permeability pulmonary edema because of aspiration of gastric contents during labor and delivery, the main treatment is supportive care. Prophylactic antibiotics have not been found to be beneficial for aspiration pneumonitis ; therefore, antibiotics should be prescribed only when infection complicates the initial chemical pneumonitis. If the patient’s clinical course suggests development of bacterial pneumonia, the choice of antibiotic should be guided by appropriate bacteriologic evaluation of respiratory secretions, pleural fluid (if present), and blood cultures. For patients who have been in the hospital for 48 hours or less, clindamycin or a β-lactam–β-lactamase inhibitor combination is a reasonable empiric choice to treat anaerobic organisms. Glucocorticoids are not recommended in the treatment of aspiration events because of a lack of benefit found by two large multicenter randomized trials . Respiratory Infections Antibacterial agents to treat pneumonia during pregnancy should be selected according to the same principles used for nonpregnant patients [4,24,25]. For community-acquired pneumonia in pregnancy, penicillins, ceftriaxone, azithromycin, and erythromycin (excluding the estolate, which is associated with an increased risk of cholestatic jaundice in pregnancy) are probably safe. Tetracycline is contraindicated because it is teratogenic and causes hepatic toxicity when administered intravenously in pregnancy. The aminoglycosides have the potential of causing eighth nerve toxicity in the fetus and should be used only when strong clinical indications exist. Clindamycin has no reported adverse fetal effects, but experience is limited and it should be used with caution. Vancomycin hydrochloride may cause fetal renal and auditory toxicity and should be used with caution, with close monitoring of serum drug levels. Clarithromycin and levofloxacin are pregnancy risk factor class C and, therefore, should be used judiciously, weighing potential risks and benefits. The predominant treatment of influenza pneumonia is supportive care, following the same practices as outlined for other causes of respiratory failure in pregnancy. The novel influenza A (H1N1) virus that appeared in 2009 is sensitive to the neuraminidase inhibitor antiviral medications such as oseltamivir and zanamivir, but it is resistant to the adamantine antiviral agents. It is recommended that pregnant women with a confirmed, probable, or suspected case of influenza A (H1N1) receive empiric institution of oseltamivir for a period of 5 or more days. Treatment should be started although results from testing are pending, because the maximal clinical benefit is seen when antiviral therapy is begun within 48 hours of the onset of symptoms [26,69]. Adamantanes are no longer recommended for influenza owing to concerns about antiviral resistance in the circulating influenza strains . Fetal side effects have not been reported with either neuraminidase inhibitor, although experience with them is limited. The recommended dosing is 10 mg per kg every 8 hours intravenously, with adjustments made for renal insufficiency. Initiation of acyclovir at the first evidence of respiratory system involvement in pregnant patients with cutaneous varicella infection optimizes the chances of a favorable outcome. Infants born to women in whom varicella infection developed within 4 days of delivery should receive varicella-zoster immune globulin within 72 hours of birth . Amphotericin B is the drug of choice for severe disseminated coccidioidal infection during pregnancy .
Although defective neutrophil function has been sought in this condition buy diclofenac online pills, it is rarely found generic 50mg diclofenac with amex. Systemic symptoms are uncommon purchase discount diclofenac online, and the onset of a fever suggests a more deeply seeded infection order cheapest diclofenac. Most patients with furuncles can be treated with warm compresses to promote spontaneous drainage. For carbuncles or furuncles in a patient with fever and/or surrounding cellulitis, antimicrobial therapy should be directed against S. Surgical drainage may be required in cases in which spontaneous drainage does not occur and antibiotic treatment does not achieve resolution of the lesion or lesions. In the presence of recurrent or continuous furunculosis, chlorhexidine solution for bathing, attention to personal hygiene, appropriate laundering of garments, bedding, and towels, and careful wound dressing procedures are recommended. Mupirocin nasal ointment or oral antibiotic regimens of rifampin (600 mg daily) plus dicloxacillin (500 mg every 6 hours) or ciprofloxacin (500 mg twice daily) for 10 days can be added to mupirocin nasal therapy, if an initial course of mupirocin is not effective. Carbuncles are larger subcutaneous abscesses that represent a progression from furuncles. For prevention, chlorhexidine solutions for personal hygiene, mupirocin to prevent nasal carriage, and prophylactic antibiotics are useful. These infections can be dangerous: a) On the face, they can lead to cavernous sinus infection. Carbuncles are the most important complication of furunculosis, and surgical intervention may be necessary for debridement of affected tissues. Furuncles involving the nose and perioral area can be complicated by cavernous sinus infection attributable to venous drainage patterns. Bacteremia with development of distant secondary sites of infection can occur (particularly if the furuncle is manipulated) and can result in considerable morbidity and mortality. Skin abscesses and carbuncles are similar histologically, but like furuncles, carbuncles arise from infection of the hair follicles. Skin abscesses can arise from infection tracking in from the skin surface, but abscesses are usually located deeper than carbuncles (ure 10. In contrast to carbuncles, abscesses can also be seen as a complication of bacteremia. Relatively minor local trauma, such as injection of a drug, can also be a risk factor. Skin abscesses can be attributed to a variety of microorganisms and may be polymicrobial; however, the most common single organism is S. The most common findings with a skin abscess are local pain, swelling, erythema, and regional adenopathy. Fever, chills, and systemic sepsis are unusual, except in patients with concomitant cellulitis. Patients may have single or multiple skin abscesses, and cellulitis around the skin abscess can occasionally occur. Skin abscess commonly involves the upper extremities in intravenous drug abusers but can be located at any anatomic site. Patients with recurrent episodes of skin abscess often suffer anxiety because of the discomfort and cosmetic effects of the infections. Results of microbiologic studies, including Gram stain and routine culture should direct subsequent treatment. The initial antibiotic therapy is identical to that for furuncles and carbuncles, except for skin abscess in the oral, rectal, and vulvovaginal areas. Infections in these sites require broader-spectrum therapy, amoxicillin– clavulanate being a suitable option for oral therapy (see Table 10. At other sites, clindamycin can be considered for initial therapy if anaerobes are a possible cause. Surgical incision and drainage can be performed if the abscess feels fluctuant or has “pointed”; spontaneous drainage can obviate the need for surgery. Although the results of testing will usually be negative, metabolic and immunologic screening should be performed in patients with recurrent furunculosis, carbuncles, or skin abscesses in the absence of another predisposing factor. These tests should include determination of fasting blood glucose and, if values from the former test are high-normal or elevated, a hemoglobin A1c should be ordered. Neutrophil number and function, plus immunoglobulin levels also should be evaluated. Elevated levels of immunoglobulin E (IgE) in association with eczema defines a Job’s (hyper- IgE) syndrome, a disease that is characterized by recurrent staphylococcal skin infections. Skin abscesses are localized infection of the dermis and subcutaneous tissue, usually deeper than carbuncles. Therapy is identical to that for furuncles and carbuncles, with these additions: a) Oral clindamycin may be considered if anaerobes are possibly involved. Preventive measures: a) With recurrent furunculosis, carbuncles, or abscesses, exclude diabetes mellitus, neutrophil dysfunction, and hyper-immunoglobulin E syndrome. Most patients with skin abscess respond to therapy and do not develop serious complications. However, bacteremia can occur, and metastatic sites of infection, including endocarditis and osteomyelitis, can develop. Individuals at high or moderate risk for endocarditis should be given antimicrobial prophylaxis before potentially infected tissue is incised and drained. Parenteral administration of an antistaphylococcal antibiotic (either oxacillin or cefazolin) is recommended as prophylactic therapy in this setting. Commercial and sports fisherman may cut a finger on a fish spine, and that injury can result in an Erysipelothrix infection. This pleomorphic gram-positive rod causes painful erythematous lesions primarily of the hands and other exposed areas. Cultures and biopsies are often negative, because the pathogen remains deep in the dermis. Penicillin is preferred for treatment, although in the penicillin- allergic patient, clindamycin or ciprofloxacin have been found to be effective. This atypical mycobacterium is found in fresh and salt water, including aquariums. Infections usually begin as small papules, but gradually expand and fail to respond to conventional antibiotics. Surgical debridement in the absence of appropriate antibiotic treatment can result in worsening of the infection. The microbiology laboratory should always be notified when atypical mycobacteria are suspected. Oral doxycycline or minocycline (100 mg twice daily), or oral clarithromycin (500 mg twice daily) for a minimum of 3 months is the treatment of choice. Waterborne pathogens and their treatments: a) Erysipelothrix (penicillin) b) Mycobacterium marinum (minocycline or clarithromycin) 2. Plant- and soil-borne pathogens and their treatments: a) Sporotrichosis (itraconazole) b) Nocardiosis (trimethoprim–sulfamethoxazole) Other atypical mycobacteria found throughout the environment can also cause indolent soft tissue infections including M. Gardeners who are cut by rosebush thorns are at risk for Sporothrix schenckii infection. Inoculation of soil into the skin as a consequence of trauma can also result in a Nocardia soft tissue infection that mimics sporotrichosis. Prolonged oral therapy with trimethoprim–sulfamethoxazole (5 mg/kg daily of the trimethoprim component, divided into two daily doses) or minocycline (100 mg twice daily) is usually curative. Tetanus Immunization policies have made tetanus an uncommon problem in the United States. Approximately 70 cases are reported annually, with most cases occurring in individuals over 60 years of age whose immunity is waning. The incidence is much higher in developing countries, resulting in 1 million cases associated with 300,000-500,000 deaths. In developed countries, most cases of tetanus are the sequelae of punctures or lacerations. This metalloprotease degrades a protein required for the docking of neurotransmitter vesicles that normally inhibit firing of the motor neurons. As a consequence, muscle spasms develop, and patients experience masseter muscle trismus (“lock jaw”) and generalized muscle spasm, including arching of the back (opisthotonus), flexion of the arms, and extension of the legs. Spasm of the diaphragm and throat can lead to respiratory arrest and sudden death. Autonomic dysfunction can lead to hypertension or hypotension, and bradycardia or tachycardia. Neonatal tetanus develops following infection of the umbilical stump and is most commonly reported in developing countries.
In developing countries order 50mg diclofenac overnight delivery, treatment with vitamin A has been associated with a 50% reduction in the mortality of severe measles cheap 100mg diclofenac otc. Hospitalized children with measles in the United States often have a measurable deficiency in vitamin A order generic diclofenac from india, and they are more likely to have pneumonia or diarrhea purchase diclofenac 50 mg without prescription. The World Health Organization recommends vitamin A therapy for all children with measles, and the American Academy of Pediatrics recommends vitamin A therapy for hospitalized children older than 2 years with measles in the United States . Data for older children and adults are lacking, but vitamin A treatment should probably be provided for all individuals with severe measles [59,60]. Intravenous ribavirin was reported to have beneficial effects in a small case series of measles pneumonia in adults , but there are no data from prospective randomized studies. Less frequent bacterial causes of pneumonia following measles include Neisseria meningitidis, Klebsiella pneumoniae, Escherichia coli, Haemophilus influenzae, and Pseudomonas species . Intravenous ribavirin was beneficial when given early to patients with another hantavirus disease, hemorrhagic fever with renal syndrome caused by Hantaan virus . Recommendations are to fluid resuscitate with 1 to 2 L of isotonic crystalloid and then maintain as low a wedge pressure (8 to 12 mm Hg) as is compatible with satisfactory cardiac output (cardiac index 2 more than 2. Although prospective clinical trials have not been performed, the current recommendation is that patients with suspected influenza A H5N1 infection promptly receive a neuraminidase inhibitor, preferably within 48 hours of infection [6,69]. Emergence of resistance to oseltamivir has been documented in a few patients with H5N1 infections treated with oseltamivir . Whether combination therapy with zanamivir or other antivirals is beneficial and would reduce the emergence of oseltamivir resistance is unknown. The influenza A H5N1 isolates from Asia are highly resistant to the adamantanes, and therefore these drugs do not play a therapeutic role . Corticosteroids have been used in the treatment of sporadic influenza A H5N1 infections, but their routine use cannot be recommended. Efforts to reduce transmission to healthcare workers and other patients are often guided by the transmission efficiency of the specific viral agents. The New World hantaviruses are generally not transmitted person to person, except possibly the Andes virus. Strategies to prevent nosocomial transmission include isolation precautions for patients, chemoprophylaxis and immunization of healthcare workers if possible, and surveillance and rapid identification of healthcare workers’ exposures. In general, patients with suspected epidemic viral pneumonias should be housed with a combination of standard, contact, droplet, and airborne isolation precautions. When feasible, limit the number of healthcare workers with direct access to the patient and limit their contact with other patients. If high-efficiency masks are limited or unavailable, surgical masks may be considered if the primary mode of agent transmission is via droplets and no aerosol-generating procedures are performed. Advances of antiviral or immunomodulatory therapy of viral pneumonias based on randomized controlled trials or meta-analyses of such trials is summarized in Table 83. Rubeola (measles) Oral vitamin A therapy decreases mortality and improves recovery from pneumonia in children [58,59]. Shiraishi K, Mitamura K, Sakai-Tagawa Y, et al: High frequency of resistant viruses harboring different mutations in amantadine-treated children with influenza. Puhakka T, Lehti H, Vainionpaa R, et al: Zanamivir: a significant reduction in viral load during treatment in military conscripts with influenza. Kaiser L, Wat C, Mills T, et al: Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Jefferson T, Jones M, Doshi P, et al: Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. Kiso M, Mitamura K, Sakai-Tagawa Y, et al: Resistant influenza A viruses in children treated with oseltamivir: descriptive study. South East Asia Infectious Disease Clinical Research Network: Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial. Ribaud P, Scieux C, Freymuth F, et al: Successful treatment of adenovirus disease with intravenous cidofovir in an unrelated stem-cell transplant recipient. Tatsukawa M, Sawayama Y, Nabeshima S, et al: A case of severe adult measles pneumonia—efficacy of combination of steroid pulse therapy, high-dose vitamin A and gamma globulins. Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, et al: Human disease from influenza A (H5N1), Thailand, 2004. The virion is enveloped with cellular membrane and is formed of the virus-encoded structural proteins, of which spike (S) protein is the main attachment factor responsible for entry of the virion into the host cell . The first confirmed case was in November 2002, after which it spread around the world to 26 countries, causing 8,096 confirmed cases and 774 deaths (a case fatality rate of 9. There is also evidence that dromedary camels (Camelus dromedaries) act as an intermediate between bats and humans [17,18]. Camels are an extremely important species in the Middle East, where they are a source of meat, fabric, and milk, and camel racing is an important part of the cultural and economic development in the region. There is also evidence of edema and the alveolar septa were thickened with lymphocytes (but not plasma cells), neutrophils, and macrophages . Gender, specifically being male, is excluded from the table, as this factor has been specifically identified with access to dromedary camels [36,39]. It is also important to establish a clear infection control plan for use in the hospital setting, including rapid diagnostic and safety protocols . Korea Centers for Disease Control and Prevention: Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea, 2015. Hauser G, Awad T, Brok J, et al: Peginterferon plus ribavirin versus interferon plus ribavirin for chronic hepatitis C. The size and worldwide nature of this outbreak demonstrates that health care facilities require protocols for the care of patients who might be or are definitively harboring Biosafety Level 4 agents such as Ebola. The following chapter will review special considerations for the diagnosis and care of patients with Ebola virus infection. Given its similar taxonomy and clinical features, the principles discussed here almost certainly apply in like manner to patients suffering from Marburg virus disease, which since its original episode in Germany has not been observed outside of sub-Saharan Africa, but is equally likely to present off the African continent given the ease and increase of international travel. The transmission of Ebola primarily takes place by direct contact with body fluids, where virions enter into the host via mucous membranes or skin breaks . Incubation of the virus typically lasts between 2 and 21 days; most cases present in the second week following exposure . The relatively long incubation times coupled with highly efficient transcontinental travel underscores the importance of heightened surveillance and the need for health care facilities everywhere to have response plans in place. Therefore, patients from Ebola-endemic countries presenting with circulatory collapse in the setting of a febrile illness may require rapid isolation and testing for Ebola and Marburg. This, in turn, may lead to gut translocation of gram-negative organisms, potentially leading to bacterial sepsis as a major cause of mortality . Other common early symptoms include fatigue, arthralgias and myalgias, anorexia, headache, and abdominal pain. A diffuse, erythematous nonpruritic maculopapular rash was only rarely reported in the West African Outbreak, although it appeared to have been more prevalent among the whites who became infected and thus may have been underdiagnosed in Africans with darker skin . If the patient is no longer symptomatic after 72 hours, repeat testing is not required; however, patients with ongoing symptoms must be retested. Potassium regulation can be difficult, as one study indicated that equal numbers of patients developed hypo- or hyperkalemia . Hiccups may also be seen and should prompt suspicion in the setting of other appropriate epidemiologic clues . Coupled with insensible losses from fevers, the significant fluid depletion often leads to circulatory collapse and likely accounts at least in part for the high mortality of the disease. The prevalence of bleeding of any kind before the West African Outbreak was reported to be in the range of approximately 50%; during the West African Outbreak, at least one study reported a prevalence of less than 20% . Studies in previous outbreaks indicated that, although less common, hemorrhage was typically associated with a worse prognosis . Similarly, mental status changes such as encephalopathy probably reflects end-organ damage and carries a high mortality. While many patients experience rapid improvement, they remain viremic for as long as 21 days or more . Therefore, provisions need to be made for convalescing patients who must remain in isolation during this time, and psychosocial needs may outweigh physiologic considerations, as survivors commonly cope with fear, grief, and anxiety about the social stigma that may await them following discharge . Following discharge, patients experience a range of complications that can be debilitating and last for months or even years. The persistence of Ebola virus in immunologically privileged “sanctuary” sites, such as semen  and ocular fluid , indicates that special precautions must be taken when evaluating survivors in routine follow-up care, with Biosafety Level 4 protocols being used in the event that providers might be exposed to fluids from these viral reservoirs. In critical care settings, the need for safety protocols is even greater due to the larger number of opportunities for occupational exposure.
However generic diclofenac 50mg fast delivery, because some patients cheap diclofenac 50 mg visa, especially those with severe exacerbations cheap diclofenac 100 mg with mastercard, may be unable to perform the necessary testing maneuvers purchase diclofenac 50 mg otc, the physician also must be adept at recognizing certain historical features and physical findings that strongly suggest high risk for severe airway obstruction. A recent history of poorly controlled asthma (increases of dyspnea and wheezing, frequent nocturnal awakenings due to shortness of breath, increased use of β- adrenergic rescue medications, increased diurnal variability of peak expiratory flow, and recent hospitalizations or emergency department visits) and any history of a prior near-fatal asthma exacerbation (prior admission to an intensive care unit or intubation for asthma) are the most important predictors of a patient’s propensity for severe life- threatening asthma exacerbations [1,2,34–37]. Current or recent use of oral corticosteroids, not currently using inhaled corticosteroids, a history of psychosocial problems, poor adherence with asthma medications, and a history of food allergies are other warnings that the patient is at risk of asthma-related death [1,2]. Patient complaints of severe breathlessness or chest tightness or difficulty walking more than 100 feet (30. Cigarette smoking also has been associated with higher in-hospital and posthospitalization mortality . In general, patients are somewhat better judges of the severity of their airway obstruction during an attack of asthma than are physicians who elicit their history at the bedside . However, the patient’s own assessment of airway obstruction should never be the exclusive means of assessing the severity of airway obstruction. Notably, patients with a history of severe asthma sometimes have a blunted perception of dyspnea [40,41]. When assessing risk for fatal asthma, other important historical details include identification of current medications and coexisting illnesses, such as psychiatric disease, that interfere with medical follow- up and cardiopulmonary disease. A history of known coronary artery disease is important because the patient may be more sensitive to the stimulatory effects of β2-adrenergic agonists and to the cardiac complications of hypoxemia. These patients may also be receiving β2- adrenergic antagonists that are making control of their asthma worse. Physical Examination Physical examination is important for excluding other causes of dyspnea (see Differential Diagnosis section) and assessing the degree of airway obstruction. Tachycardia (greater than 120 beats per minute), tachypnea (greater than 30 breaths per minute), diaphoresis, bolt-upright posture in bed, pulsus paradoxus greater than 10 mm Hg, and accessory respiratory muscle use all should be regarded as signs of severe airway obstruction . However, because the absence of these signs does not rule out severe obstruction, physical examination cannot be relied on exclusively to estimate the severity of airway obstruction. The amount of wheezing heard on auscultation of the chest is a notoriously poor method of assessing the severity of airway obstruction . Pulmonary Function Tests To evaluate a patient who is having an acute exacerbation of asthma, an objective measure of maximal expiratory airflow should be performed [1,2]. An exception to this is the patient who is unable to perform a testing maneuver due to a severe, life-threatening exacerbation with obvious airway compromise and cyanosis. These tests are valuable for the initial assessment and for assessing responses to therapy, especially after 1 hour of treatment . Guidelines recommend reassessment of lung function one hour after initiation of treatment and then frequent reassessments thereafter (Table 172. A partial pressure of arterial1 oxygen (PaO ) less than 60 mm Hg or a pulse oximeter oxygen saturation2 value less than 90% on room air should be regarded as additional evidence that the patient’s exacerbation is severe. With modest airway obstruction, the patient’s mild dyspnea stimulates an increase in minute ventilation that meets or exceeds the level required to maintain normal alveolar ventilation. As airway obstruction worsens,2 dyspnea becomes more severe and the central nervous system drive to increase minute ventilation becomes intense. As the airway obstruction becomes more severe and prolonged, high minute ventilation can no longer be maintained by the respiratory musculature and alveolar ventilation decreases. Any coexisting conditions (malnutrition, advanced age) or medications (sedatives) that weaken respiratory muscle function or depress respiratory drive should be expected to accelerate the onset of hypercapnic ventilatory failure during acute exacerbations of asthma. Other Laboratory Studies For acute exacerbations of asthma, routine chest radiographs reveal few abnormalities other than hyperinflation . However, although not recommended for routine assessment, for severe exacerbations chest radiography can be helpful when there is clinical suspicion of other causes of dyspnea and wheezing (see Differential Diagnosis section) or complications of severe airway obstruction . Chest radiographs should be examined for evidence of enlarged cardiac silhouette, upper lung zone redistribution of blood flow, pleural effusions, and alveolar or interstitial infiltrates because any one of these findings suggests a diagnosis other than or in addition to acute asthma. In addition, chest radiography allows the early detection of common complications of severe airway obstruction, including pneumothorax, pneumomediastinum, and atelectasis. Also, lung infiltrates on chest radiographs can be compatible with a diagnosis of asthma complicated by mucoid impactions (e. Among the elderly, for patients with severe hypoxemia, and for individuals with suspected cardiac ischemia or arrhythmias, an electrocardiogram should be performed. This initial assessment and repeated objective measures of airway obstruction guide treatment that combines supportive measures, bronchodilator therapy, and anti-inflammatory therapy (Table 172. Because corticosteroids take at least 4 to 6 hours to begin to have a beneficial effect and many of the inflammatory causes of airway obstruction may take days to resolve, the medical challenge is to support patients until the inflammatory processes have responded to corticosteroids. Although these bronchodilators relieve only one component of the airway obstruction during severe exacerbations of asthma, even small improvements of airflow can lead to important clinical benefits in the acute setting. Of the available bronchodilators, β2-adrenergic agonists are the most effective and rapidly acting and, therefore, most useful during that critical time before the onset of corticosteroid action . Other measures that support the patient until the inflammatory processes in the airways have resolved include supplemental oxygen, judicious fluid administration, and, when indicated, mechanical ventilation. Although the primary cellular target of β2-adrenergic agonists is airway smooth muscle, other cell types in the airways also express β2-adrenergic receptors that may regulate mediator release by mast cells, epithelial cells, and nerves. These short-acting agents are rapidly acting with an onset of action less than 5 minutes and are the mainstay of bronchodilator therapy for acute asthma, especially albuterol [1,2]. The potential advantage of this preparation is that the S-enantiomer present in racemic albuterol does not contribute to bronchodilation and might have deleterious effects on the airways. However, there have not been large, randomized, double-blind, and controlled trials in adults to show that this theoretical concern is clinically important. Moreover, a systematic review and meta-analysis of smaller studies concluded that levalbuterol was not superior to albuterol with respect to either efficacy or safety in the treatment of acute asthma exacerbations . The major side effects of β2-adrenergic agonists during the treatment of severe asthma exacerbations are tremor, cardiac stimulation, hypokalemia, and hyperlactatemia [52,54]. These side effects are potentially serious, especially in the elderly, who frequently have underlying cardiac disease. Cardiac toxicity can be minimized by using agonists with high β2-adrenergic receptor selectivity, by avoiding systemic administration of β2-adrenergic agonists, and by maintaining adequate oxygenation . Numerous studies have shown that the bronchodilator effects of inhaled β2-adrenergic agonists are rapid in onset and equal to the effect achieved by systemic delivery . Because the inhaled route allows administration of comparatively small doses directly to the airways with minimal systemic toxicity, this route is almost always preferable to systemic delivery [1,2]. Frequent, multiple inhalations of the medication may allow for progressively deeper penetration of the drug into peripheral airways. In fact, continuous administration by nebulizer may be more effective for severely obstructed patients [59,60]. Because of its lower density than oxygen, helium–oxygen (heliox)– powered nebulizer treatments have the potential to improve penetration of aerosols into the lungs. However, a systematic review with meta- analysis comparing heliox versus air–oxygen driven nebulization found no support for helium-powered nebulization in the routine care of acute exacerbations of asthma . Theoretically, systemic administration of β-adrenergic agonists could deliver drugs via the bloodstream to obstructed airways that are poorly accessible to inhaled aerosols. More selective β2-adrenergic agonists, such as terbutaline, are available for subcutaneous use, but cardiac toxicity among elderly individuals is still a significant concern even with these more selective agents. However, intravenous delivery of β2-adrenergic agonists is no longer recommended for the routine treatment of even severe exacerbations of asthma [1,2]. No convincing evidence has shown intravenous administration to be superior to inhaled delivery of β2- adrenergic agonists [56,62]. Both the lack of enhanced efficacy and the potential cardiac toxicity of intravenous β2-adrenergic agonists have led most authorities to reserve intravenous delivery for those rare adult patients, closely monitored, who continue to deteriorate on mechanical ventilation despite maximal routine therapy with inhaled β2-adrenergic agonists. It is important to emphasize again that intravenous β2- adrenergic agonists are not recommended in guidelines and are unlikely to be any more effective than inhaled β2-adrenergic agonists such as albuterol [1,2]. Exceptions may be bronchospasm induced by acetylcholinesterase inhibitors or β2-adrenergic antagonists and patients with severe cardiac disease who are unable to tolerate β2-adrenergic agonists. However, inhaled cholinergic antagonists have a low incidence of side effects and are a recommended adjunct to β2-adrenergic agonists for the initial treatment of severe exacerbations of asthma [1,2,65,66]. Because even small improvements of airway caliber could prove clinically significant for the severely obstructed and deteriorating patient, it is recommended that ipratropium be routinely added to β2-adrenergic agonist therapy during the initial treatment of severe asthma exacerbations in the emergency department  (see Management section). However, inhaled ipratropium bromide currently is not recommended for routine use once a patient is hospitalized with a severe exacerbation of asthma [1,2].