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Clinical Practice Guideline for the 65 Oros D order zithromax 500mg visa, ueras F zithromax 500mg generic, Cruz‐Martinez R buy 100 mg zithromax, Meler E, Management of Women who Report Decreased Fetal Munmany M, Gratacos E. Umbilical and fetal middle cerebral in computerized fetal heart rate analysis antepartum. Fetal perception of reduced fetal movements: a prospective biophysical profile scoring: a prospective study in cohort study. Best Pract Res Clin Obstet Doppler ultrasound in predicting the perinatal Gynaecol 2017;38:12–23. Biophysical adverse pregnancy outcome: systematic review and profile for fetal assessment in high risk pregnancies. Doppler ultrasonography in 71 American College of Obstetricians and Gynecologists’ high‐risk pregnancies: systematic review with meta‐ Committee on Practice Bulletins—Obstetrics. Changes definition of macrosomia through an outcome‐based in fetal Doppler indices as a marker of failure to reach approach in low‐ and middle‐income countries: a growth potential at term. Stillbirth in gestation, increased intrapartum operative intervention diabetic pregnancies. Placental syndromes: getting to 64 Cruz‐Martinez R, Savchev S, Cruz‐Lemini M, Mendez the heart of the matter. Intrapartum clinical, sonographic, and perinatal outcome in small‐for‐gestational‐age fetuses. Ultrasonographic weight estimation in large for the value of ultrasound in the prediction of successful gestational age fetuses: a comparison of 17 sonographic induction of labor. Ultrasound 89 Garcia‐Simon R, ueras F, Savchev S, Fabre E, Obstet Gynecol 2013;41:398–405. Performance of the outcome after labor induction for late‐onset small‐for‐ ultrasound examination in the early and late third gestational‐age fetuses. Ultrasound Obstet Gynecol trimester for the prediction of birth weight deviations. Validation of Induction of labour at or near term for suspected fetal models that predict Cesarean section after induction macrosomia. Prior to this the fetus relies on placental trans­ able to cross the placenta and stimulate the fetal thyroid fer of maternal thyroid hormones. It has been estimated that (T3) increase with advancing gestation, from 14–16 weeks neonatal thyrotoxicosis occurs in 2–10% of babies born onwards [1,2]. The T3 concentrations are lower than adult levels throughout placenta is more permeable to IgG in the second half of pregnancy. As a result, of the fetal pituitary–thyroid axis is independent of the fetal hyperthyroidism usually develops in the second half mother. Disruption of normal 1) Euthyroid, not on medication, but who has previously thyroid function, if unrecognized and untreated, can received antithyroid drugs: the risk of fetal/neonatal therefore have significant long‐term sequelae. More commonly it occurs second­ 2) Euthyroid, previously treated with radioactive iodine ary to maternal thyroid disease and/or its treatment. High concentrations of antibodies identify mass, such as cystic hygroma, cervical teratoma and hae­ a pregnancy at risk of fetal hyperthyroidism. The goitre may repre­ should be measured again in the third trimester to sent fetal hyperthyroidism or hypothyroidism. There may be tachycardia or bradycar­ can cause hyperextension of the fetal neck resulting in dia and in severe cases complete heart block. Fetal hypo­ in polyhydramnios with its associated risk of preterm thyroidism is often unrecognized and should be consid­ labour. Management Ultrasound can detect fetal goitre, which is the earliest Management ultrasound feature of fetal thyroid dysfunction and If fetal hypothyroidism is secondary to maternal antithy­ appears before fetal tachycardia. Colour flow the fetal thyroid should be carried out at no greater than Doppler may help differentiate between a hyperthyroid fortnightly intervals to ensure reduction in size, which is and a hypothyroid goitre. Hyperthyroidism is associated usually noted within 2 weeks of reducing therapy [8]. In at‐risk pregnancies monthly used and 250–500µg of T4 at 7–10 day intervals is a ultrasound should be carried out from around 20 weeks’ proposed regimen [9]. If the fetal condi­ Cordocentesis is the only direct method of assessing tion deteriorates despite treatment, cordocentesis is fetal thyroid function. Treatment by maternal administration of antithyroid ● Fetal goitre, present on ultrasound, indicates fetal drugs is both safe and effective in the management of thyroid dysfunction if other differential diagnoses fetal hyperthyroidism. If the ● It should be possible to distinguish fetal hyperthy- mother is euthyroid she may require thyroxine supple­ roidism from hypothyroidism on clinical grounds in mentation. Fetal hypothyroidism Worldwide, iodine deficiency is the leading cause of fetal hypothyroidism. Five enzymes are responsible for the conversion of tibodies can cause fetal hypothyroidism. Anti‐thyroper­ cholesterol to cortisol, and a defect in any one of these oxidase antibodies cross the placenta in the third will cause precursors to be diverted to the production of trimester but have little effect on fetal thyroid function. Androgen excess in utero leads to virilization of a echocardiography are the main diagnostic techniques. Androgen reader is referred to other literature for a more compre­ excess does not affect development of fetal male genitalia. The aim of therapy is to prevent virilization of a female Irregular fetal heart rate fetus. The fetal adrenal gland can be suppressed by maternal administration of dexamethasone. A minimum This is typically described as a ‘missed beat’ and is usually dose of 20 µg per kilogram pre‐pregnancy weight in two due to atrial extrasystoles. These extrasystoles are more divided doses is the recommended regimen and therapy common in the third trimester and are detected in 1. Occasionally (2–3% of cases) a sustained tachycardia develops and it is wise to auscultate Approach to management the heart regularly to ensure this does not occur. Atrial fibrillation and chaotic atrial tachycardia are much ● Discontinue dexamethasone in all male fetuses and all less common and ventricular tachycardia is extremely rare unaffected female fetuses. Information regarding longer‐term effects is lim­ Atrial flutter ited and parents must be made aware of this when the atrial rate is very fast at 350–500 bpm. Fetal dysrhythmias Management options These comprise irregular fetal heart rhythm, fetal tachy­ the fetus with a sustained tachycardia is at risk of devel­ cardias and fetal bradycardias. Delivery, followed by postnatal therapy, is an interval and this cannot be detected on routine ultra­ option if close to term, but it is recognized that pharma­ sound. In utero therapy is effective until an impulse is blocked; this results in an irregular in restoring sinus rhythm and is the preferred option for rhythm but the fetal heart rate may be normal. On M‐mode the atrial rate may be twice that the transplacental route is the route of choice for of the ventricular rate (2 : 1 block) and occasionally 3 : 1 fetal therapy. Digoxin atrial isomerism and congenitally corrected transposi­ can be given as a loading dose, 0.

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Antibiotics metabolized primarily by the liver should generally be avoided or reduced in patients with significant cirrhosis discount 100 mg zithromax visa. In patients with significant renal dysfunction buy discount zithromax on line, antibiotic doses need to be modified purchase zithromax online pills. Patients who have just arrived in the hospital tend to be colonized with community-acquired pathogens; patients who have been in the hospital for prolonged periods and have received several courses of antibiotics tend to be colonized with highly resistant bacteria and with fungi. The severely ill patient who is toxic and hypotensive requires broad-spectrum antibiotics; the patient who simply has a new fever without other serious systemic complaints can usually be observed off antibiotics. Within 3-4 days following the administration of antibiotics, sequential cultures of mouth flora reveal that the numbers and types of bacteria begin to change significantly. The normal flora die, and resistant gram-negative rods, gram-positive cocci, and fungi begin to predominate. The more quickly the selective pressures of broad-spectrum antibiotic coverage can be discontinued, the lower the risk of selecting for highly resistant pathogens. Broad coverage is reasonable as initial empiric therapy until cultures are available. By the third day, the microbiology laboratory can generally identify the pathogen or pathogens, and a narrower- spectrum-specific antibiotic regimen can be initiated. Despite the availability of culture results, clinicians too often continue the same empiric broad- spectrum antibiotic regimen, and that behavior is a critical factor in explaining subsequent infections with highly resistant superbugs. Continuing broad-spectrum antibiotics beyond 3 days drastically alters the host’s resident flora and selects for resistant organisms. Use narrower-spectrum antibiotics to treat the specific pathogens identified by culture and Gram stain. All Else Being Equal, Choose the Least Expensive Drug As is discussed in later chapters, more than one antibiotic regimen can often be used to successfully treat a specific infection. Given the strong economic forces driving medicine today, the physician needs to consider the cost of therapy whenever possible. Too often, new, more expensive antibiotics are chosen over older generic antibiotics that are equally effective. In this book, the review of specific antibiotics is accompanied by cost range estimates to assist the clinician in making cost-effective decisions. For example, the acquisition cost of gentamicin is low, but when blood-level monitoring, the requirement to closely follow blood urea nitrogen and serum creatinine, and the potential for an extended hospital stay because of nephrotoxicity are factored into the cost equation, gentamicin is often not cost-effective. Take into account the specific host factors: a) Immune status b) Age c) Hepatic and renal function d) Duration of hospitalization e) Severity of illness. Switch to a narrower-spectrum antibiotic regimen based on culture results within 3 days. He defervesced, and secretions from his endotracheal tube decreased over the next 3 days. However, because the sputum culture was positive for Candida albicans, the physician added an antifungal agent, fluconazole. One of the most difficult and confusing issues for many physicians is the interpretation of culture results. Once a patient has been started on an antibiotic, the bacterial flora on the skin and in the mouth and sputum will change. Often, these new organisms do not invade the host, but simply represent new flora that have colonized these anatomic sites. Too often, physicians try to eradicate the new flora by adding new more-powerful antibiotics or antifungal agents. The eventual outcome can be the selection of a bacterium or fungus that is resistant to all anti-infective agents. No definitive method exists for differentiating between colonization and true infection. In the absence of these findings, colonization is more likely, and the current antibiotic regimen should be continued. Fortunately, Candida never spreads from the mouth to cause pneumonia in patients with normal immune systems, and therefore this organism should be ignored when it grows from sputum samples. Evidence for a new superinfection includes a) new fever or a worsening fever pattern, b) increased peripheral leukocyte count with left shift, c) increased inflammatory exudate at the original site of infection, d) increased polymorphonuclear leukocytes on Gram stain, and e) correlation between bacterial morphology on Gram stain and culture. Clinicians should be familiar with the general classes of antibiotics, their mechanisms of action, and their major toxicities. The differences between the specific antibiotics in each class can be subtle, often requiring the expertise of an infectious disease specialist to design the optimal anti-infective regimen. The general internist or physician-in-training should not attempt to memorize all the facts outlined here, but rather should read the pages that follow as an overview of anti-infectives. The chemistry, mechanisms of action, major toxicities, spectrum of activity, treatment indications, pharmacokinetics, dosing regimens, and cost are reviewed. Upon prescribing a specific antibiotic, physicians should reread the specific sections on toxicity, spectrum of activity, pharmacokinetics, dosing, and cost. Because new anti-infectives are frequently being introduced, prescribing physicians should also take advantage of handheld devices, online pharmacology databases, and antibiotic manuals so as to provide up- to-date treatment (see Further Reading at the end of the current chapter). When the proper therapeutic choice is unclear, on-the-job training can be obtained by requesting a consultation with an infectious disease specialist. Anti-infective agents are often considered to be safe; however, the multiple potential toxicities outlined below, combined with the likelihood of selecting for resistant organisms, emphasize the dangers of overprescribing antibiotics. The side chain attached to the β-lactam 1 ring (R ) determines many of the antibacterial characteristics of the specific antibiotic, and the structure of the side chain attached to the dihydrothiazine ring (R ) determines the pharmacokinetics and metabolism. Penicillins, cephalosporins, and carbapenems are all β-lactam antibiotics: a) All contain a β-lactam ring. The inhibition of these transpeptidases prevents the cross- linking of the cell wall peptidoglycans, resulting in a loss of integrity of the bacterial cell wall. Without its protective outer coat, the hyperosmolar intracellular contents swell, and the bacterial cell membrane lyses. The activity of all β-lactam antibiotics requires active bacterial growth and active cell wall synthesis. Therefore, bacteria in a dormant or static phase will not be killed, but those in an active log phase of growth are quickly lysed. Bacteriostatic agents slow bacterial growth and antagonize β-lactam antibiotics, and therefore, in most cases, bacteriostatic antibiotics should not be combined with β-lactam antibiotics. Toxicities of β-Lactam Antibiotics Hypersensitivity reactions are the most common side effects associated with the β-lactam antibiotics. Penicillins are the agents that most commonly cause allergic reactions, at rates ranging from 0. Allergic reactions to cephalosporins have been reported in 1-3% of patients, and similar percentages have been reported with carbapenems. However, the incidence of serious, immediate immunoglobulin E (IgE)-mediated hypersensitivity reactions is much lower with cephalosporins than with penicillins. Approximately 1-7% of patients with penicillin allergies also prove to be allergic to cephalosporins and carbapenems. Penicillins are the most allergenic of the β-lactam antibiotics because their breakdown products, particularly penicilloyl and penicillanic acid, are able to form amide bonds with serum proteins.

The brain is edematous and shows a leptomeningeal inflammatory reaction and cortical surface petechiae cheap zithromax 100 mg online. The fat emboli are more prevalent in the gray matter best zithromax 500mg, but the hemorrhages are more common in the centrum semiovale; internal capsule; and cerebral and cerebellar white matter [53] order zithromax 100 mg mastercard. Electron microscopy reveals intravascular fat vacuoles; breakdown of endothelial walls; swollen neurons; and glia [53]. Diagnosis Characteristically, there is a symptom-free interval of 12 to 48 hours between the inciting trauma and the onset of fat embolism syndrome [46]. Altered consciousness or development of neurologic deficits after a lucid interval following trauma should alert the physician to the possibility of fat embolism. The syndrome may present as a spectrum of disability, from subclinical presentations with only a decreased arterial partial pressure of oxygen (PaO ), decreased platelets or hemoglobin, to a2 fulminant presentation. Gurd’s diagnostic criteria for fat embolism syndrome include one or more major criteria (respiratory insufficiency, neurologic dysfunction, or petechial rash), four or more minor criteria (fever, tachycardia, retinal changes, jaundice, or renal changes), and one or more laboratory criteria (fat macroglobulinemia, decreased hemoglobin or platelets, or increased erythrocyte sedimentation rate) [47]. An alternative diagnostic scheme was proposed by Schonfeld [47], assigning a numerical score to similar criteria with a score of 5 or more suggestive of the diagnosis. Respiratory distress and hypoxemia with an oxygen tension less than 60 mm Hg is common and may be the initial or only laboratory abnormality. The chest radiograph may be unremarkable for one-half of the cases, but fine stippling or hazy infiltrates of both lung fields should be sought, because they are consistent with fat embolism syndrome [51]. Petechiae are present in 50% to 60% of clinically recognized cases and are most often found on the lower palpebral conjunctivae; neck; anterior axillary folds; and anterior chest wall [47]. There is an associated thrombocytopenia, believed to be caused by the consumption of platelets with their aggregation around the embolic fat droplets, and a progressive anemia with hemoglobin levels commonly less than 9. The retinal emboli appear as small rosaries of microinfarcts surrounding the macula of both eyes, which over the course of the following 10 to 14 days evolve into yellowish, fatty plaques [51]. The symptoms can begin with restlessness and confusion and may evolve gradually or abruptly to stupor and coma. Decerebrate rigidity is found in up to 15% of cases, and pyramidal signs of hyperreflexia and extensor plantar responses are found in 30% to 70%. Focal neurologic signs, such as aphasia and hemiparesis, are usually restricted to patients with more severe disturbances of consciousness [47]. These range from acute findings of scattered embolic appearing ischemia to chronic changes with demyelinating changes and atrophy. Treatment Rapid immobilization of fractures and their early definitive management decreases the likelihood of fat embolism syndrome [51]. Sequential clinical examinations, chest radiographs, and arterial blood gas determinations for patients believed to be at high risk may help identify early on those needing more aggressive care. These patients should have early and expedient replacement of fluids and blood and administration of 40% oxygen by mask [51]. The support of respiration and maintenance of arterial oxygen levels greater than 70 mm Hg sometimes requires intubation and mechanical ventilation. Steroids have been advocated as treatment to blunt the inflammatory response, to help preserve vascular integrity, and to minimize interstitial edema formation, but there are as yet no controlled trials demonstrating a consistent benefit. Prognosis Mortality in fat embolism syndrome can reach 10% to 20%, but recent improvements in management have lessened this rate [57]. A favorable prognosis is more likely with normal muscle tone, active deep tendon reflexes, and retention of appropriate pain response [47]. Prolonged hiccups can produce fatigue, sleeplessness, weight loss, depression, difficulty in ventilation, and, in postoperative patients, wound dehiscence [58]. In intubated patients, persistent hiccups may result in hyperventilation and respiratory alkalosis [58]. Pathophysiology Hiccups result from a sudden reflex contraction of the diaphragm, causing forceful inspiration, which is arrested almost immediately by glottic closure, producing the characteristic sound. The efferent pathway includes the phrenic nerve to the diaphragm, the vagus nerve to the larynx, and the spinal nerves to the accessory muscles of inspiration. Although central control of this reflex is not well defined, it probably involves lower brainstem and upper cervical spinal levels, including the respiratory center, phrenic nerve nuclei, medullary reticular formation, and hypothalamus [59]. Etiology Hiccups may result from a multitude of causes, owing to injury or irritation of the afferent or efferent pathways or disease within the central control mechanism. Hiccups most frequently result from irritation of the stomach wall or diaphragm, leading to impulses along the phrenic and vagus nerves. Abdominal disorders causing hiccups include gastric ulceration, gastric distention, gastroesophageal reflux, hiatus hernia, cholecystitis, peritonitis, subdiaphragmatic abscess, ileus, and bowel obstruction. Thoracic disorders that precipitate hiccups include esophagitis, pericarditis, myocardial infarction, pneumonia, and neoplasm. More proximally along the course of the nerves, neck masses, such as neoplasm and goiter, may also result in hiccups. Perioperative causes include neck extension, intubation, visceral traction, and intraoperative manipulation of efferent or afferent nerves [58]. Metabolic disorders, such as uremia, electrolyte abnormalities, alcohol intoxication, diabetes mellitus, and general anesthesia, have also been implicated [58,59]. Hiccups have been reported in four patients with Parkinson’s disease, and dopamine agonists appeared to play a causative role [63,64]. Chest and abdominal radiographs are obtained routinely, and fluoroscopic evaluation of the diaphragm is sometimes needed. Other investigations include determinations of electrolytes, renal function, glucose, creatine kinase (if myocardial infarction is suspected), and a toxicology screen for alcohol and barbiturates. Management Initial management includes identification and treatment of disorders that may cause hiccups, such as inflammation, infection, or gastric dilatation. When this is unsuccessful, nonpharmacologic and pharmacologic treatments are available for intractable hiccups. Pharyngeal stimulation may resolve hiccups, either by nasogastric intubation, swallowing dry granulated sugar, or by the introduction of a red rubber catheter through the mouth or nares, followed by a jerky to-and-fro movement [58]. Counterstimulation of the vagus nerve by pressure on eyeballs, rectal massage, or irritating the tympanic membrane may also alleviate hiccups [59]. Breathing into a paper bag, gasping with fright, Valsalva maneuver, and supramaximal inspiration possibly abolish hiccups by interrupting the stimulus for respiration or increasing the carbon dioxide concentration [65]. Baclofen 5 mg orally three times a day, increased to 10 mg three times a day, has been effective in decreasing and potentially eliminating hiccups [59]. Alternatively, chlorpromazine taken 25 to 50 mg orally or intramuscularly three or four times a day has also been effective. If this is ineffective in 2 to 3 days, then a slow intravenous infusion of chlorpromazine 25 to 50 mg in 500 to 1,000 mL of normal saline is indicated. Other medications used in refractory patients include haloperidol (5 mg three times per day), anticonvulsants (e. In refractory cases, transcutaneous stimulation of the phrenic nerve, transesophageal diaphragmatic pacing, vagus nerve stimulation, phrenic nerve block or ablation, or microvascular decompression of the vagus nerve may be useful [60,66,67]. Because there are multiple efferent pathways involved, hiccups may remain even after phrenic nerve ablation. The ulnar nerve may be compressed in the condylar groove posterior to the medial epicondyle when the arms are positioned in a flexed, pronated, or semipronated fashion, or when the flexed elbows are used by the patient for repositioning.

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Aggressive management with cardiopulmonary bypass with external cooling of the blood may be necessary when dantrolene fails to slow down thermogenesis promptly [113] purchase 250mg zithromax otc. When patients respond to therapy quickly purchase zithromax 100mg with visa, before severe temperature elevation occurs cheap zithromax online amex, only minimal supportive measures may be necessary. Procainamide acts to increase the uptake of calcium from the myoplasm directly and in early stages may help reduce hyperthermia. Avoid dopaminergic and α- agonists because they reduce heat dissipation owing to peripheral vasoconstriction. Prophylactic treatment with phenobarbital is strongly recommended because seizures may increase heat production, metabolic acidosis, and hypoxia. Mannitol and furosemide may be needed to promote continued urine output and may reduce the likelihood of cerebral edema and acute tubular necrosis. The variation reflects differences among the populations sampled, surveillance methods, and definitions of the disease. Two prospective series reported 24 and 68 cases, with mortality rates of 0% [124] and 5% [125], respectively. Because the syndrome is found among patients on dopamine receptor blockade agents or inpatients after withdrawal of dopaminergic agents (Table 185. Butyrophenones [126–140], phenothiazines [126,128,131,134,141,142], thioxanthenes [143–145], and dibenzoxazepines [146] are believed to act as dopamine receptor– blocking agents. Drugs acting at the D dopamine–binding sites appear to have the2 greatest potential for causing the syndrome. Most cases occur among patients taking butyrophenones or piperazines, agents with a high incidence of extrapyramidal reactions. Abrupt withdrawal of levodopa (L-dopa), dopa-carbidopa, or amantadine produced the syndrome in patients suspected of having Parkinson’s disease [153–155]. Initiation of metoclopramide therapy has produced the syndrome, presumably owing to alteration in central dopaminergic tone [156–158]. A peripheral muscle abnormality is possible because the sarcoplasmic calcium concentration is higher among patients who have had the syndrome [125], resolves with nifedipine use [159], and has been reported to be triggered by hypoparathyroidism [160]. However, the muscular effects are typical of the parkinsonian type of extrapyramidal reactions, frequently seen at low therapeutic doses soon after treatment begins, and the muscle spasm resolves with the use of centrally acting dopaminergic agents such as bromocriptine, amantadine, and L-dopa. The fact that the degree of temperature increase varies directly with the severity of rigidity evident on examination strongly suggests that muscle contracture is responsible for increased thermogenesis [126]. A decrease in muscle rigidity by uncoupling contraction with dantrolene or by paralysis with succinylcholine results in a decrease in temperature [161]. Impaired heat dissipation from the anticholinergic-induced hypohidrosis of neuroleptics may also occur. The most likely hypothesis is that regulatory reflexes remain intact, but muscle rigidity from the hypothalamus and subsequent increased thermogenesis exceed dissipative capacity. This allele is2 associated with reduced density and function of dopamine receptors as well as decreased dopaminergic activity and metabolism [239]. Clinical Presentation Onset of symptoms may occur within hours after the initial neuroleptic treatment or up to 4 weeks later [162]. Among the majority of cases, onset occurs within 1 week from initial neuroleptic drug use, and 88% occur within 2 weeks of a dosage increase of an already prescribed neuroleptic agent [162]. Most cases have a slow progression of symptoms over at least 24 to 48 hours and last 2 weeks after stopping the inciting drug [171]. Early symptoms include dysphagia or dysarthria, pseudo- Parkinsonism, dystonia, or catatonic behavior. In one series, 96% of patients demonstrated rigidity, 92% of patients demonstrated tremor, and 96% of patients demonstrated muteness or hypophonia in the 48 hours before diagnosis [124]. Rigidity precedes hyperthermia in 59% of patients, is concurrent in 23%, and is subsequent in only 8%. Elevations in creatinine kinase and transaminase levels and leucocytosis parallel the body temperature. Cardiovascular collapse, renal failure, and electrolyte abnormalities are less common and less severe than in classic heat stroke. Renal failure is owing to myoglobin- induced acute tubular necrosis and the dehydration that results from diaphoresis. Renal dysfunction of most patients is transient and mild and, even among cases with acute tubular necrosis, and may return to premorbid values after brief periods of dialysis support [129]. Although death from cardiovascular collapse has been reported [126], specific cardiac abnormalities have been poorly described. The white blood cell count is elevated 3 among 78% of cases [124,162], usually less than 20,000 cells per mm, 3 and rarely exceeding 25,000 cells per mm. Thrombotic events, when they do occur, may be a result of the patient’s immobility owing to coma and muscle rigidity rather than to any temperature-mediated change. Mild elevations of lactate dehydrogenase, serum glutamic oxaloacetic acid transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase are common. This criterion requires independent validation before its use can be recommended in clinical practice. Differential Diagnosis A thorough examination and diagnostic evaluation for other causes of hyperthermia should be conducted (see Table 185. Acute lethal catatonia presents with psychotic excitement and automatisms a few weeks before motor deficit [174]. If catatonia has been induced or exacerbated by neuroleptics, withdrawal of the neuroleptic drug should aid in clarifying the diagnosis. Heat stroke must be considered when temperature elevation develops in a patient taking neuroleptics during periods of high ambient temperature or after vigorous exercise. In the rare circumstance in which the two syndromes cannot be distinguished, attempts at paralysis with curare or pancuronium may aid diagnosis. Idiosyncratic drug reactions and anaphylaxis accompanying severe hyperthermia may usually be diagnosed by their distinct clinical presentations. Monoamine oxidase inhibitors may produce hyperthermia, especially when administered with meperidine, linezolid, or dextromethorphan [177–180]. Specific agents used to decrease thermogenesis by reducing muscle contracture include dantrolene, curare, pancuronium, amantadine, bromocriptine, and L-dopa (Table 185. Dantrolene therapy does carry a risk of hepatotoxicity, but in patients with temperatures greater than 40°C, its use is specific and should be beneficial. Paralysis with curare or pancuronium should produce a similar prompt decrease in temperature, but this treatment necessitates mechanical ventilation and extensive support [161]. Bromocriptine, amantadine, and carbidopa/L-dopa increase central dopaminergic tone; this decreases the central drive, reducing muscular rigidity and thermogenesis. The use of dantrolene, bromocriptine, and amantadine has yet to be shown to reduce mortality significantly [123]. Electroconvulsive therapy has been successful for several patients [131,132,189,190] and is the only therapeutic modality that may be used successfully to treat simultaneously hyperthermia, the extrapyramidal side effects, and the underlying neuropsychiatric disorder for which the neuroleptic drug was prescribed. Because of several reports of cardiovascular collapse among patients undergoing electroconvulsive therapy, this therapy should be given only to patients at low risk of cardiovascular disease who have failed other therapy. Less-specific agents, such as diphenhydramine, benztropine, diazepam, and trihexyphenidyl, have been used successfully [127,130,134,137,139,146] but more typically have not been helpful [121,134,140,141,161,187,188]. Rechallenge with neuroleptics may cause the syndrome to recur, but this occurs much more frequently during the first 2 weeks [201,202], concomitant use of lithium, high potency drugs, and parenteral neuroleptics.