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Chapter 5 Echocardiography in Infective Endocarditis Diagnosis Maria Teresa Gonzàlez-Alujas and Artur Evangelista Masip Introduction Early and reliable diagnostic and risk stratification strategies are critical to reduce delays in the initiation of appropriate antimicrobial therapy and identify patients who require urgent valve surgery order levitra professional 20mg without prescription. Moreover buy generic levitra professional 20 mg on line, Doppler echocardiography provides clinically important information on the presence and degree of valvular destruction and their haemodynamic consequences buy levitra professional 20mg low cost, as well as on the existence of perivalvular infection generic levitra professional 20 mg with amex. Three echocardiographic findings were considered to be major criteria for the diagnosis of endocarditis: (a) presence of vegetations defined as mobile echodense masses implanted in a valve or mural endocardium in the trajectory of a regurgitant jet or implanted in prosthetic material with no alternative anatomical explanation; (b) presence of abscesses; or (c) presence of a new dehiscence of a valvular prosthesis. Abnormal echocardiographic findings not fulfilling these definitions were consid- ered minor criteria. Since the definitive diagnosis of endocarditis requires the presence of two major criteria or one major and three minor criteria, it is clear that echocardiography has assumed a crucial role in the diagnosis of the disease, particularly when blood cultures are negative. Evangelista Masip , PhD Servei de Cardiologia , Hospital Universitari Vall d’Hebron , Barcelona , Spain e-mail: teresagonzalu@gmail. Typically, a vegetation presents as an oscillating mass attached to a valvular structure, with a movement independent of that of this valve (Table 5. A vegetation may also present as a non-oscillating mass and with an atypical location. Vegetations are usually located on the atrial side of the atrio-ventricular valves and on the ventricular side of the aortic and pulmonary valves. Less fre- quently, vegetations are located on papillary muscles or mural endocardium. Over time, vegetations tend to decrease in size with therapy, although they may persist indefinitely as less mobile and more echogenic masses. Vegetations persisting after effective treatment must not be interpreted as a clinical recurrence of the disease unless supported by clinical features and bacteriological evidence. For instance, in sys- temic lupus erythematosus inflammatory mass lesions (Libman-Sacks) related to 5 Echocardiography in Infective Endocarditis Diagnosis 39 Fig. Other sterile vegetations, such as in marantic endocarditis, may also be present in patients with advanced malig- nancies. A mass effect may be seen in patients with myxomatous valves, ruptured chordae unrelated to infection or heart tumours. Appropriate use of echocardiography using simple clinical criteria improves the diagnostic yield. An exception is in patients with staphylococcus aureus bacteraemia when routine echo is warranted owing to the aggressiveness of this infection. This study underlines the importance of recognising the phase of the disease in which the study is performed since vegetations may not be large enough to be visualised when endocarditis is suspected very early on. The sewing ring and support structures of mechanical and bioprosthetic valves are strongly echogenic and may prevent vegetations detection within the valve apparatus or its shadow. The vegetative growth appears as thickening and irregularity of the normally smooth contour of the sewing ring. Both thrombus and pannus have a similar appearance and cannot be distinguished from vegetative material. Strands are commonly 5 Echocardiography in Infective Endocarditis Diagnosis 41 Fig. Bioprosthetic valve leaflets may become infected with secondary destruction of leaflet tissue. The distinction between wear-and-tear degeneration of tissue valves and endocarditis is often difficult. In addi- tion, when vegetations were visualised, it was difficult to determine whether tri- cuspid valve endocarditis, lead infection or both were present. Negative Blood Culture Endocarditis In those cases, echo is crucial in the diagnosis of infectious endocarditis. The two main causes of negative blood culture endocarditis are: previous antibiotic treat- ment or infection by fastidious microorganisms, with limited capability for growth in conventional culture media (Fig 5. Abscess Formation and Paravalvular Extension of Infection The second major echocardiographic criterion for endocarditis is the presence of perivalvular abscesses. Perivalvular abscesses are considered to be present when a definite region of reduced echo density, without colour flow detected inside, is found on the echocardiogram (Fig. Sensitivity and specificity of 5 Echocardiography in Infective Endocarditis Diagnosis 43 Fig. Pseudoaneurysm is characterised anatomically by a perivalvular cavity commu- nicating with the cardiovascular lesion. The echocardiographic hallmark of pseu- doaneurysm is the presence of a pulsatile perivalvular echo-free space with colour Doppler within. The echocardiographic appearance of partial systolic collapse proves that the abscess communicates with the cardiovascular lumen (Fig. Perivalvular cavities are formed when annular infections break through and spread into contiguous tissue. In native aortic valve endocarditis, the generally occur through the weakest portion of the annulus, which is near the membranous septum. The abscess can expand to form a pseu- doaneurysm and can subsequently cause a perforation and communication between the left ventricle and left atrium. An intervalvular pseudoaneurysm was defined as an echo-free cavity located posteriorly in the intervalvular fibrosa region, just below the aortic annulus, and bound by the base of the anterior mitral leaflet, the medial wall of the left atrium and the posterior aortic root (Fig. Both aortic root abscesses and pseudoaneurysms may rupture into adjacent cham- bers and therefore create intracardiac fistulous tracts (Fig. These fistulae may be single or multiple and generally extend from the aorta to the right ventricle or the right or left atrium [15]. Using colour Doppler, the site of the com- munication of the ruptured intervalvular pseudoaneurysms is usually well defined. By continuous-wave Doppler, systolic high-velocity flow suggests an abnormal communication between the aorta and either the left or right atria. Dehiscence is generally defined fluoroscopically as a rock- ing motion of the prosthetic valve more than 15° in any one plane. This complication may lead to a gross separation of the prosthetic annulus from the native tissue. Diagnosis of Other Complications Valvular Complications Regurgitation of the infected valve is almost constant and results from a variety of mechanisms. Some degree of valvular destruction is commonly seen and may vary from a small perforation in a cusp to a complete flail leaflet. Valvular perforation is a frequent complication that may cause severe insufficiency with acute onset and pre- cipitate heart failure (Fig. In aortic endocarditis cusp perfora- tion, flail or both may occur in up to 50% of cases. Severe aortic insufficiency as estimated by Doppler has been associated with poor prognosis. In this setting, early diastolic closure of the mitral valve identifies patients with unstable haemodynamic status. Perforation of the mitral leaflets is less common, occurring only in 15% of patients with mitral valve endocarditis (Fig. Progressive destruction of the mitral valve results initially in ruptured chordae tendinae and ultimately flail leaflet. Colour flow Doppler imaging permits the location of abnormal flows in the areas of ana- tomic interruption and therefore aids the differentiation between mitral cusp perfo- ration and true mitral regurgitation. The presence of a new or increasing paravalvular regurgitation or valve dehiscence is a major criterion for the diagnosis 5 Echocardiography in Infective Endocarditis Diagnosis 47 A Fig. The demonstra- tion of aortic prosthetic paravalvular regurgitation is rather easy from the precor- dium as the colour-encoded regurgitant jets may be visualised from both the apical and parasternal views. Echocardiography plays a key role in the management of these complications by aiding decision-making regarding valve sur- gery and its optimal timing. Perivalvular extensions, discussed previously, are present in around 20% of cases and indicate valve surgery owing to the risk of heart failure due to prosthetic valve dehiscence, fistulae or persistence of infection [18 ]. Embolic events are frequent and are symptomatic in around 20–25% of cases and silent in almost 50 %. The risk of embolization appears much greater for mitral than for aor- tic valve endocarditis. The rate of embolic events declines rapidly after the initiation of effective antibiotics, dropping from an initial 13 events per 1000 patients-days in the first week to less than 1.

The collective data that are currently available in literature do not support the withdrawal of these drugs from the practice of neonatal anesthesia purchase levitra professional 20 mg. The neurotoxicity data seem to be reproducible in rodents but not in other species order levitra professional discount. Future prospective trials with prospective neurocognitive testing of infants exposed to anesthesia are needed buy genuine levitra professional on line. There currently exists no conclusive evidence to demonstrate the deleterious effect of inhaled or intravenous 2990 anesthetics on neurocognitive function in neonates and infants generic 20mg levitra professional overnight delivery. Prospective studies, including a current study randomizing infants to getting a spinal anesthesia versus general anesthesia should be able to provide better information on this very complex problem that may face pediatric anesthesiologists. There has been a strong trend in recent years to put an emphasis of presurgical stabilization before taking the newborn to the operating room. Exceptions to this include gastroschisis, which is usually corrected within 12 to 24 hours, airway lesions such as webs that are causing significant airway obstruction, and acute subdural/epidural hematomas from traumatic delivery. In most cases, however, a period of 1 to 3 days can be allowed for stabilization of the newborn or transport to an appropriate pediatric center for treatment. There is more to neonatal emergency surgery than just the immediate anesthetic and surgical procedures. Many of these infants require the support services of specialized nursing units, pediatric radiologists, pediatric intensive care physicians, specialized laboratory facilities, and they must have their complete care be the main consideration of where their surgery should be done. Many procedures are now performed using laparoscopic techniques which decreases postoperative morbidity and pain and facilitates early extubation. Because of the lack of expertise many hospitals have in the care of these patients, the transfer of these neonates to hospitals with greater expertise is often prudent after initial stabilization of the patient. Most hospitals that have expertise in these patients have a transport team that is well-qualified to help with stabilization and transport. Those centers that do not have transport teams often have extensive protocols and procedures to work with the sending institution to help ensure the safe transfer of the patient. Two confounding factors in neonatal surgery are prematurity and associated congenital anomalies. The presence of one congenital anomaly 2992 increases the likelihood of another one. A neonatologist should be consulted in the case of any neonate with a congenital defect who is considered for surgery. The most serious associated congenital lesion is that of the cardiovascular system. The new strategy of permissive hypercapnia and delayed surgical repair has resulted in survival rates of more than 75% in some centers. Embryology Early in fetal development, the pleuroperitoneal cavity is a single compartment. The gut is herniated or extruded to the extraembryonic coelom during the ninth to tenth weeks of fetal life. During this period, the diaphragm develops to separate the thoracic and abdominal cavities (Fig. If there is delay or incomplete closure of the diaphragm, or if the gut returns early and prevents normal closure of the diaphragm, a diaphragmatic hernia will develop, producing varying degrees of herniation of the abdominal contents into the chest. The left side of the diaphragm closes later than the right side, which results in the higher incidence of left-sided diaphragmatic hernias (foramen of Bochdalek). Approximately, 90% of hernias detected in the first week of life are on the left side. Clinical Presentation The clinical presentation and the outcome from a diaphragmatic hernia are varied. The bowel contents may compress the lung buds and prevent development, leading to bilateral hypoplastic lungs with very little chance for 2993 survival. In most instances, however, a moderately small diaphragmatic hernia may develop later in fetal life so the lung is normal but compressed by the abdominal viscera. At the mild end of the scale, the infant might have a relatively normal pulmonary vascular bed with varying degrees of persistent pulmonary hypertension that may rapidly revert to normal. In more severe defects, significant pulmonary hypoplasia and abnormal pulmonary vasculature lead to greater mortality, largely a result of ongoing pulmonary hypertension. After closure of the pleuroperitoneal membrane, muscular development of the diaphragm occurs. Incomplete muscularization of the diaphragm results in the development of a hernia sac because of intra-abdominal pressure. The condition is known as eventration of the diaphragm, and the diaphragm may extend well up into the thoracic cavity. The other possibility is that the innervation of the diaphragm is incomplete and the muscle is atonic. Eventration of the diaphragm is usually not symptomatic in the first week of life. Various factors have been proposed to identify predictability of survival, including early gestation diagnosis, severe mediastinal shift, polyhydramnios, a small lung-to-thorax transverse area ratio, and the herniation of liver or stomach. B: The pleuroperitoneal folds have fused with the septum transversum and the mesentery of the esophagus in the seventh week, thus separating the thoracic cavity from the abdominal cavity. C: In a transverse section at the fourth month of development, an additional rim derived from the body wall forms the most peripheral part of the diaphragm. At times, the degree of interference is so great that the neonate’s clinical condition begins to deteriorate immediately and, in other situations, it may be several hours before the infant’s condition is fully appreciated. In the severely affected newborn, the initial clinical findings are usually classic and readily discerned. The infant has a scaphoid abdomen secondary to the absence of intra-abdominal contents, which have herniated into the chest. Immediate supportive care entails tracheal intubation and control of the airway along with decompression of the stomach. Excessive airway pressure carries a high risk for pneumothorax before and after the repair. The thought was that removing the abdominal viscera from the thorax would allow for re- expansion of the atelectatic lung and improved oxygenation. The use of aggressive ventilation strategies to induce respiratory alkalosis has been abandoned secondary to the high incidence of iatrogenic lung injury. These have been well demonstrated in animal experiments when compared with tracheal ligation. Despite a period of preoperative stabilization, some infants still have a component of reactive pulmonary hypertension. The goals of ventilatory management are to ensure adequate oxygenation and avoid barotrauma. Any sudden deterioration in oxygen saturation with or without associated hypotension should raise suspicion of pneumothorax. It is important to avoid hypothermia because this increases the oxygen requirement and could precipitate pulmonary hypertension. Blood loss and fluid shifts are usually not a problem, although maintenance of intravascular volume is essential to avoid acidosis, which could also precipitate pulmonary hypertension. In those infants who will remain intubated after surgery, inhalation agents and narcotics may be used as tolerated. In those infants with a small defect, who present to the operating room with little or no respiratory distress, it may be beneficial to avoid intraoperative narcotics and provide regional or neuraxial analgesia in anticipation of extubation. The use of nitrous oxide should be avoided, particularly in those situations in which abdominal closure could be difficult. Recovery depends on the degree of pulmonary hypertension and pulmonary hypoplasia. It was previously believed that pulmonary hypoplasia was responsible for most deaths; however, it is now believed that potentially reversible pulmonary hypertension may be responsible for as much as 25% of reported deaths. B: The complete repair with Gore-Tex graft material and the liver appropriately located in the abdominal cavity. Relative left ventricular hypoplasia with an attenuated muscle mass and cavity size have been described. Omphalocele and Gastroschisis Although omphalocele and gastroschisis sometimes appear similar and may be confused, they have entirely different origins and associated congenital anomalies. Failure of part of or all the intestinal contents to return to the abdominal cavity results in an omphalocele that is covered with a membrane called the amnion (Fig. Gastroschisis, in contrast, develops later in fetal life, after the intestinal contents have returned to the abdominal cavity.

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The cerebral computed tomography scan generic levitra professional 20mg line, performed 1 day later buy 20 mg levitra professional visa, demonstrated the development of intracerebral and intraventricular hemorrhage (d) buy generic levitra professional 20 mg. Embolic complications may also be asymptomatic in about 20% of patients and only be detected by systematic imaging [5 ] order levitra professional 20 mg free shipping. Several studies evaluated the value of echocardiography for predicting embolic events (Table 11. In a multicenter prospective study , vegetation length 11 Embolic Complications in Infective Endocarditits 139 140 D. Kang >10 mm and mobility of vegetation were predictors of new embolic events, and vegetation length >15 mm was a predictor of mortality in multivariable analysis. A recent multicenter cohort study also confirmed that vegetation length >10 mm was the most potent independent predictor of new embolic events [10 ]. Other factors associated with increased risk of embolism include previous embo- lism [15], infection with particular microorganism [3 , 8, 9] and involvement of the mitral valve [8, 16] (Table 11. Six variables associated with embolic risk were used to create the calculator: age, diabetes, atrial fibrillation, previous embolism, vegetation length >10 mm and Staphylococcus aureus infection. Rapid initiation of antibiotic therapy is also effective in preventing embolism [7 – 10], and several studies evaluated the effects of medical and surgical treatment on embolic compli- cations (Table 11. In another multicenter cohort study , 86% of neurologic complications were observed before or during the first week of antibiotic therapy, with the incidence of neurologic complications markedly decreasing after appropriate antimicrobial ther- apy. Because embolic risk decreases rapidly before vegetation size is significantly reduced, it is quite possible that the salutary effects of antibiotics on embolization may be related to their early effects on molecular and cellular milieu of the vegeta- tion. The incidence of 40 embolic events was highest during the first 2 weeks after the initiation of 30 antibiotic therapy (44. With permission from 10 Elsevier Limited) 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Week of antibiotic therapy and congestive heart failure [13, 14, 18, 20], but indications for surgical intervention to prevent systemic embolism remain to be defined [14 , 18]. Early identification of patients at high risk of embolism [3, 6], increased experience with complete exci- sion of infected tissue and valve repair, and low operative mortality have raised arguments for early surgery [13, 21], but there have been concerns that such surgery may be more difficult to perform in the presence of active infection and inflamma- tion, which leads to a high operative mortality and a high risk of postoperative valve dysfunction [22]. Consensus guidelines for performance of early surgery on the basis of vegetation were different (Fig. Since the benefits of surgery to prevent embolism are greatest during the first week of the diagnosis, deferring surgery after 1 to 2 weeks is of little value [8, 13]. Patients in the early surgery group underwent surgery within 7 days of diagno- sis (median interval, 2. Previous observational studies compar- ing outcomes between surgery versus medical therapy were subject to the limitations of baseline differences, treatment selection and survivor biases [11 , 24–28 ] and recent studies using propensity scoring models yielded conflicting results on the benefits of surgery [11, 24–27]. Although prospective, randomized trials may reduce differences in patient characteristics and these biases between treatment groups, ethical, logistical and financial constraints have deterred us from conducting a ran- domized trial. The major hypoth- esis of this trial was that early surgery would decrease the rate of death or embolic events, as compared with conventional treatment. All patients in the early surgery group underwent valve surgery within 48 h after randomization. Of the 39 patients in the conventional treatment group, 30 (77 %) patients underwent surgery during initial hospitalization (n = 27) or during follow-up (n = 3). However, this trial was limited in scope and excluded patients with major stroke, prosthetic valve endocarditis or aortic abscess and the incidence of S. There was no significant between-group difference in all-cause mortality at 6 months (a). The potential benefits of surgery need to be weighed against its operative risks and long-term consequences. Surgical option to prevent embolism is indi- cated when embolic risk exceeds operative risk of the individual patient and the benefit of surgery would be greater if conservative procedure preserving the native valve is likely or severe valvular regurgitation is associated. Conclusion Echocardiography plays a key role in assessing embolic risk and patients with large vegetations are at higher risk of embolism. The decision for surgery should be based on individual risk-benefit analysis, and early surgery is strongly indicated if embolic risk exceeds operative risk. Risk of embolism and death in infective endocarditis: prognostic value of echocardiography: a prospective multicenter study. Neurologic manifestations of infective endocar- ditis: a 17 year experience in a teaching hospital in Finland. Risk factors, outcome and impact of cardiac surgery: a multicenter observational study. Prediction of symptomatic embolism in infective endo- carditis: construction and validation of a risk calculator in a multicenter cohort. Impact of early surgery on embolic events in patients with infective endocarditis. Risk of embolization after institution of antibi- otic therapy for infective endocarditis. Stroke location, characterization, severity and outcome in mitral vs aortic valve endocarditis. A randomized trial of aspirin on the risk of embolic events in patients with infective endocarditis. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the 148 D. Kang Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. The timing of surgery influences mortality and morbid- ity in adults with severe complicated infective endocarditis: a propensity analysis. Impact of valve surgery on 6-month mortality in adults with complicated, left-sided native valve endocarditis: a propensity analy- sis. The impact of valve surgery on 6-month mortality in left-sided infective endocarditis. Analysis of the impact of early surgery on in- hospital mortality of native valve endocarditis: use of propensity score and instrumental vari- able methods to adjust for treatment-selection bias. The association between the timing of valve surgery and 6-month mortality in left-sided infective endocarditis. Staphylococcus aureus native valve infective endocar- ditis: report of 566 episodes from the International Collaboration on Endocarditis Merged Database. The Society of Thoracic Surgeons 2008 cardiac surgery risk model, part 2: isolated valve surgery. Impact of cerebrovascular complications on mor- tality and neurologic outcome during infective endocarditis: a prospective multicenter study. Several fac- tors associated with higher risk of embolism or neurological complications have been identified including presence, size and mobility of vegetations on echocardiog- raphy, S. The clinical picture, however, is often is characterised by one type of neurological sign U. Snygg-Martin 12 Neurological Complications in Infective Endocarditis 151 or even the absence of neurological symptoms, i. Encephalopathy with impaired consciousness and meningism has also been argued to be of septic embolic origin [8, 19]. Embolic risk is reported to be age dependent by some authors [24], but results are conflicting and different risk estimates can be explained in a time-dependent manor with lower risk of embolic events in older patients in the pre- diagnostic and early treatment phase counteracted by higher risk in the late treat- ment and follow up period, relative to an age-dependent and comorbid related risk of stroke [13 ]. Studies not primarily focusing on neurological complications [25 , 26] or with a narrow definition of neurological complications as strictly of embolic cerebrovascu- lar origin, e. Higher numbers are reported in criti- cally ill patients requiring intensive care admission [28]. Snygg-Martin attention and in three out of four patients suffering neurological symptoms, these are evident at the time of presentation [5 , 20 , 31]. Although neurological complications with clinical symptoms are pre-treatment manifestations in most patients, new neurological symptoms, first time or recurrent, during antibiotic therapy occur in a substantial proportion of patients. Any type of clinically evident embolic manifestation is an important risk factor for a subsequent neurological complication, thus warranting close follow up with antibiotic optimi- sation if possible, new echocardiographic investigation and a surgical re-evaluation. Growing evidence also supports the predictive value of silent cerebral lesions to predict embolic risk [32]. Regardless of type of neurological symptoms most abnormalities are small isch- aemic lesions being more frequent than large infarctions [29]. Multifocal infarctions are also common and frequently involve the end arterial territories of cerebral vessels [2 , 33, 34]. It is, however, surprisingly uncommon that these infected emboli give rise to intracerebral infections such as meningitis, infectious aneurysms or brain abscesses, possibly related to the effective protection the blood-brain barrier exhibits to haematogenous bacterial seeding. The clinical syndromes seen with punctuate cerebral infarctions are variable and often referred to as an altered level of consciousness or embolic encephalopathy without reported incidence of concomitant focal or multifocal neu- rological signs [35]. The three underlying mechanisms of haemorrhage are pyogenic arteritis and erosion of the arterial wall causing intracerebral bleed- ing, haemorrhagic transformation of an initially purely ischaemic infarction and rupture of infectious (mycotic) aneurysm with subarachnoidal and/or intracere- bral bleeding [38, 39].

Clinical Pearls • The simplicity of this technique is offset by the potentially significant risk of systemic local anesthetic toxicity if the tourniquet fails or is released prematurely buy levitra professional 20 mg overnight delivery. Complications related to systemic toxicity include seizures order 20 mg levitra professional with amex, cardiac arrest generic 20 mg levitra professional with visa, and death; other noted complications include nerve damage levitra professional 20mg with amex, compartment syndrome, and thrombophlebitis. Systemic blood levels are time-dependent, and careful attention should be paid to the sequence of tourniquet release and to patient monitoring during this period. A separate intravenous site for injection of resuscitation drugs is needed, as is ready availability of all appropriate resuscitative equipment. With careful attention to these details, this is one of the most effective and reliable technique available to the anesthesiologist. This is particularly relevant when either a narrow band of anesthesia (intercostal or paravertebral) or reduced motor block is preferable. In addition, epidural injection may be hazardous because of infection or coagulopathy. Epidural anesthesia also carries concerns of systemic hypotension and epidural hematoma, which can limit its use for some patients. The sympathetic nerves separate from their somatic counterparts early in their course, which makes independent somatic and sympathetic blockade a practical consideration. Likewise, although paravertebral blocks may result in both somatic and sympathetic blocks, hemodynamic responses are often less than those encountered during epidural block. Sympathetic blocks are performed commonly at the major ganglia, particularly the stellate, celiac, and lumbar plexus. These blocks may require multiple injections and are technically more difficult than axial anesthesia, but they offer advantages in certain clinical situations. Ilioinguinal and iliohypogastric nerve blocks are used for procedures in the inguinal area, including hernia repair and orchidopexy. A lumbar plexus block is not optimal in these cases since these nerves exit the plexus more cranially (L1–L2) than those nerves targeted by the lumbar plexus block (L3–L5). Approaches to the rectus sheath block targets the terminal branches of the 9th, 10th, and 11th intercostal nerves within the rectus sheath; ideally, injection is between the posterior rectus sheath and the rectus abdominis muscle. The initial technique of multiple injections of local anesthetic in the abdominal wall was modified to a single injection using the landmark technique by locating the “lumbar triangle of Petit. Intercostal nerve blockade is used for various conditions of acute and chronic pain affecting the thorax and upper abdomen (e. It can be performed through several means, including continuous infusions into the subpleural space, through interpleural catheters, and by direct intercostal nerve block. These nerve blocks involve injections along the easily palpated sharp posterior angulation of the ribs, which occurs between 5 and 7 cm from the midline in the back. The blocks may be performed more laterally (8 to 10 cm from the midline)144 or more medially (immediately beyond the transverse processes). The levels of T1–T5 may be most amenable to paravertebral block due to the overlying scapula and bulky paraspinal musculature at this region. Establishing blockade of five or six levels of intercostal nerves is a useful anesthetic procedure for providing analgesia and motor relaxation for upper abdominal procedures such as cholecystectomy and gastric surgery. Unilateral blockade of these nerves is a useful treatment for the pain of rib fracture and also serves to reduce postoperative analgesia requirements in patients with subcostal incisions. Several segments must be blocked in each of these applications because of the overlap in supply of the intercostal nerves. This technique is also useful in reducing the pain associated with the insertion of chest tubes or percutaneous biliary drainage procedures. For intercostal blocks, the patient may be in the lateral, sitting, or prone position. A pillow is placed under the abdomen to provide slight flexion of the thoracic spine. The arms are draped over the edge of the stretcher or operating table so that the scapula falls away laterally from the midline. Most anesthesiologists prefer to stand on the side that allows their dominant hand to hold the syringe at the caudad end of the patient. The reader is referred to the Clinical Anatomy section (see earlier) for descriptions of the locations of the relevant landmarks. The ribs are then identified along the line of their most extreme posterior angulation. The 6th and 12th ribs are marked first at their inferior borders, and a line is drawn between these two points. The rest of the ribs between them are identified, 2424 and a mark is placed on the inferior border of each rib along the angled parasagittal plane identified by the first line between the 6th and 12th ribs. After aseptic preparation, light sedation is provided for the patient, and a skin wheal is raised at each mark on the inferior border of each respective rib. Starting with the lowest rib, the index finger of the cephalad hand retracts the skin above the identifying mark in a cephalad direction. After contact is made with the rib, the cephalad traction is slowly released, the cephalad hand takes over the needle and syringe, and the needle is allowed to “walk” down to below the rib at the same angle. The needle is inserted at the intersection of the lower border of the rib and the mid-axillary line or posterior axillary line in children below 10 years old and above 10 years old, respectively. Once in the groove, aspiration is performed, and 3 to 5 mL of local anesthetic solution (lower volumes for children <3 years old) is injected. The needling and injection procedure is repeated for each segmental level and for both sides if applicable. Since the intercostal space is highly vascularized, local anesthetics are absorbed rapidly, and toxic levels of local anesthetic may be encountered when using large volumes, which can quickly lead to neurologic or cardiovascular sequelae. The rib will appear as a hyperechoic line casting a hypoechoic bony shadow underneath (Fig. Clinical Pearls • Intercostal nerve blocks can be supplemented by a number of somatic paravertebral nerve blocks or sympathetic block of the celiac plexus. Care should be taken to adjust the total dose of drug in these combined 2425 techniques so that the maximal recommended amounts are not exceeded. This depends primarily on maintaining strict safety features of the described technique. Emphasis should be placed on absolute control of the syringe and needle at all times, particularly during injection. Overdose can lead to airway obstruction and respiratory depression in the prone position. Attention must be paid to the patient’s mental status because this block produces the highest blood levels of local anesthetics compared to any other regional anesthetic technique. When the block is performed for postoperative pain relief, the dose should be reduced to 0. Respiratory insufficiency can also be seen if the intercostal muscles are blocked in a patient who depends on them for ventilation. Patients with chronic obstructive disease with ineffective diaphragm motion are not good candidates for this technique. Figure 36-26 Arrangement of relevant anatomy for ultrasound-guided intercostal nerve block. The ultrasound image shows the hyperechoic lines of the ribs casting a 2426 hypoechoic bony shadow. The pleura is the hyperechoic line deep to that of the ribs and has a glittery appearance, especially on respiration. Paravertebral Block Techniques Paravertebral block is useful for segmental anesthesia, particularly of the upper thoracic segments. It is also useful if blockade more proximal (central) than that of the intercostal nerves is needed, such as to relieve the pain of herpes zoster or a proximal rib fracture. Thoracic paravertebral block is used for breast surgery and perioperatively for thoracic surgery. Thoracolumbar paravertebral anesthesia is used commonly for inguinal herniorrhaphy and postoperative analgesia following hip surgery. Lumbar paravertebral blockade has been used successfully for outpatient hernia operations, providing significant postoperative analgesia. Single-injection paravertebral block used for surgical anesthesia has been shown to surpass general anesthesia with respect to postoperative pain relief, incidence of vomiting, and pain upon mobilization.

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As ether was easy to prepare and administer cheapest levitra professional, anesthetics were performed in Britain levitra professional 20 mg cheap, France buy generic levitra professional line, Russia purchase 20mg levitra professional with amex, South Africa, Australia, and other countries almost as soon as surgeons heard the welcome news of the extraordinary discovery. Even though surgery could now be performed with “pain put to sleep,” the frequency of operations did not rise rapidly, and several years would pass before anesthesia was universally recommended. Chloroform and Obstetrics James Young Simpson was a successful obstetrician in Edinburgh, Scotland, and among the first to use ether for the relief of labor pain. Dissatisfied with ether, Simpson soon sought a more pleasant, rapid-acting anesthetic. He and his junior associates conducted a bold search by inhaling samples of several volatile chemicals collected for Simpson by British apothecaries. Simpson and his friends inhaled it after dinner at a party in Simpson’s home on the evening of November 4, 1847. They promptly fell unconscious and, when they awoke, were delighted with their success. Within 2 weeks, he submitted his first account of its use for publication in The Lancet. In the 19th century, the relief of obstetric pain had significant social ramifications and made anesthesia during childbirth a controversial subject. Simpson argued against the prevailing view, which held that relieving labor pain opposed God’s will. The pain of the parturient was viewed as both a component of punishment and a means of atonement for Original Sin. Less than a year after administering the first anesthesia during childbirth, Simpson addressed these concerns in a pamphlet entitled Answers to the Religious Objections Advanced Against the Employment of Anaesthetic Agents in Midwifery and Surgery and Obstetrics. In it, Simpson recognized the Book of Genesis as being the root of this sentiment and noted that God promised to relieve the descendants of Adam and Eve of the curse. In addition, Simpson asserted that labor pain was a result of scientific and anatomic causes and not the result of religious condemnation. He stated that the upright position of humans necessitated strong pelvic muscles to support the abdominal contents. As a result, he argued that the uterus necessarily developed strong musculature to overcome the resistance of the pelvic floor and that great contractile power caused great pain. Simpson’s pamphlet probably did not have a significant impact on the prevailing attitudes, but he did articulate many concepts that his contemporaries were debating at the time. The Queen’s consort, Prince Albert, interviewed John Snow before he was called to Buckingham Palace to administer chloroform at the request of the Queen’s obstetrician. During the monarch’s labor, Snow gave analgesic doses of chloroform on a folded handkerchief. Victoria abhorred the pain of childbirth and enjoyed the relief that chloroform provided. Snow gave that blessed chloroform and the effect was soothing, quieting, and delightful beyond measure. John Snow, already a respected physician, took an interest in anesthetic practice and was soon invited to work with many leading surgeons of the day. He had recognized the versatility of the new agent and came to prefer it in his practice. At the same time, he initiated what was to become an extraordinary series of experiments that were remarkable in their scope and for anticipating sophisticated research performed a century later. Snow realized that successful anesthetics should abolish pain and unwanted movements. He anesthetized several species of animals with varying strengths of ether and chloroform to determine the concentration required to prevent reflex movement from sharp stimuli. Snow assessed the anesthetic action of a large number of27 potential anesthetics but did not find any to rival chloroform or ether. Snow published two remarkable books, On the Inhalation of the Vapour of Ether (1847) and On Chloroform and Other Anaesthetics (1858). The latter was almost completed when he died of a stroke at the age of 45, and it was published posthumously. Anesthesia Principles, Equipment, and Standards Control of the Airway Definitive control of the airway, a skill anesthesiologists now consider paramount, developed only after many harrowing and apneic episodes spurred the development of safer airway management techniques. Preceding tracheal intubation, however, several important techniques were proposed toward the end of the 19th century that remain integral to anesthesiology education and practice. Joseph Clover was the first Englishman to urge the 62 now-universal practice of thrusting the patient’s jaw forward to overcome obstruction of the upper airway by the tongue. Clover also published a landmark case report in 1877 in which he created a surgical airway. Once his patient was asleep, Clover discovered that his patient had a tumor of the mouth that obstructed the airway completely, despite his trusted jaw-thrust maneuver. He averted disaster by inserting a small curved cannula of his design through the cricothyroid membrane. Clover, the model of the prepared anesthesiologist, remarked, “I have never used the cannula before although it has been my companion at some thousands of anaesthetic cases. The first tracheal tubes were developed for the resuscitation of drowning victims but were not used in anesthesia until 1878. The first use of elective oral intubation for an anesthetic was undertaken by Scottish surgeon William Macewan. He had practiced passing flexible metal tubes through the larynx of a cadaver before attempting the maneuver on an awake patient with an oral tumor at the Glasgow Royal Infirmary on July 5, 1878. Because topical anesthesia was29 not yet known, the experience must have demanded fortitude on the part of Macewan’s patient. Once the tube was correctly positioned, an assistant began a chloroform–air anesthetic via the tube. Unfortunately, Macewan abandoned the practice following a fatality in which a patient had been successfully intubated while awake but the tube became dislodged once the patient was asleep. After the tube was removed, an attempt to provide chloroform by mask anesthesia was unsuccessful and the patient died. An American surgeon named Joseph O’Dwyer is remembered for his extraordinary dedication to the advancement of tracheal intubation. In 1885, O’Dwyer designed a series of metal laryngeal tubes, which he inserted blindly between the vocal cords of children suffering a diphtheritic crisis. Three years later, O’Dwyer designed a second rigid tube with a conical tip that occluded the larynx so effectively that it could be used for artificial ventilation when applied with the bellows and T-piece tube designed by George Fell. The Fell– O’Dwyer apparatus, as it came to be known, was used during thoracic surgery by Rudolph Matas of New Orleans. Matas was so pleased with it that he predicted, “The procedure that promises the most benefit in preventing pulmonary collapse in operations on the chest is … the rhythmical maintenance of artificial respiration by a tube in the glottis directly connected with a bellows. From 1900 until 1912, Kuhn148 published several articles and a classic monograph, “Die perorale Intubation,” which were not well known in his lifetime but have since become widely appreciated. His work might have had a more profound impact if it had been translated into English. Kuhn described techniques of oral and nasal intubation that he performed with flexible metal tubes composed of coiled tubing similar to those now used for the spout of metal gasoline cans. After applying cocaine to the airway, Kuhn introduced his tube over a curved metal stylet that he directed toward the larynx with his left index finger. Although he was aware of the subglottic cuffs that had been used briefly by Victor Eisenmenger, Kuhn preferred to seal the larynx by positioning a supralaryngeal flange near the tube’s tip before packing the pharynx with gauze. Kuhn even monitored the patient’s breath sounds continuously through a monaural earpiece connected to an extension of the tracheal tube by a narrow tube. Intubation of the trachea by palpation was an uncertain and sometimes traumatic act; surgeons even believed that it would be anatomically impossible to visualize the vocal cords directly. This misapprehension was overcome in 1895 by Alfred Kirstein in Berlin, who devised the first direct- vision laryngoscope. Kirstein was motivated by a friend’s report that a30 patient’s trachea had been accidentally intubated during esophagoscopy. Kirstein promptly fabricated a handheld instrument that at first resembled a shortened cylindrical esophagoscope.

In nonmathematical terms order levitra professional 20mg overnight delivery, high intrinsic clearance indicates efficient hepatic elimination order 20 mg levitra professional overnight delivery. It is hard to enhance an already efficient process buy levitra professional 20mg cheap, whereas it is relatively easy to improve on inefficient drug clearance because of low intrinsic clearance purchase generic levitra professional on line. When the intrinsic clearance is low, hepatic elimination clearance is independent of liver blood flow—the drug elimination is limited by the capacity of the liver to metabolize the drug (i. In contrast, as intrinsic clearance increases, the hepatic elimination becomes more dependent on hepatic blood flow—the liver is able to metabolize all of the drug that it is exposed to and therefore only limited by the amount of drug that is delivered to the liver (i. For drugs with a high extraction ratio and a high intrinsic clearance, hepatic elimination clearance is directly proportional to hepatic blood flow. Therefore, any manipulation of hepatic blood flow will be directly reflected by a proportional change in hepatic elimination clearance (Fig. In contrast, when the intrinsic clearance is low, changes in hepatic blood flow produce inversely proportional changes in extraction ratio (Fig. Therefore, classifying drugs as having either low, intermediate, or high extraction ratios (Table 11-3), allows predictions to be made on how intrinsic hepatic clearance and hepatic blood flow affect hepatic elimination clearance. This allows gross adjustments to be made in hepatically metabolized drug dosing to avoid excess accumulation of drugs (decreased hepatic elimination without dose adjustment) or subtherapeutic dosing strategies (increased hepatic elimination without dose adjustment). When the intrinsic clearance is low, increases in hepatic blood flows cause a decrease in the extraction ratio because the liver has limited metabolic capabilities. In contrast, when the intrinsic clearance is high, the extraction ratio is essentially independent of hepatic blood flow because the liver’s ability to eliminate drug is well above the amount of drug provided by normal hepatic blood flow. Table 11-3 Classification of Drugs Encountered in Anesthesiology According to Hepatic Extraction Ratios Pharmacologic and pathologic manipulations of cardiac output, with its consequences on hepatic/splanchnic blood flow and renal blood flow, are important covariates when designing drug dosing strategies. Although the blood is rarely the site of action of drug effect, the tissue drug concentration of an individual organ is a function of the blood flow to the organ, the concentration of drug in the arterial inflow of the organ, the capacity of the organ to take up drug, and the diffusivity of the drug between the blood and the organ. In these models, body tissues are lumped4 into groups that have similar distribution of cardiac output and capacity for drug uptake. Highly perfused tissues with a large amount of blood flow per volume of tissue are classified as the vessel rich group, whereas tissues with a balanced amount of blood flow per volume of tissue are classified as the lean tissue group or fast tissue group. The vessel-poor group (slow tissue group) are comprised of tissues that have a large capacity for drug uptake but a limited tissue perfusion. Although identification of the exact organs that make up each tissue group is not possible from the mathematical model, it is apparent that the highly perfused tissues are composed of the brain, lungs, kidneys, and a subset of muscle; the fast equilibrating tissue would be consistent with the majority of muscle and some of the splanchnic bed (e. Based on these computationally and experimentally intense physiologic models, Price4,18 was able to demonstrate that awakening after a single dose of thiopental was primarily a result of redistribution of thiopental from the brain to the muscle with little contribution by distribution to less well- perfused tissues or drug metabolism. This fundamental concept of redistribution applies to all lipophilic drugs and was not delineated until an accurate pharmacokinetic model had been constructed. Perfusion-based physiologic pharmacokinetic models have provided significant insights into how physiologic, pharmacologic, and pathologic distribution of cardiac output can effect drug distribution and elimination. Drug concentrations in the blood are used to define the relationship between dose and the time course of 668 changes in the drug concentration. The compartments of the compartmental pharmacokinetic models cannot be equated with the tissue groups that make up physiologic pharmacokinetic models because the compartments are theoretical entities that are used to mathematically characterize the blood concentration profile of a drug. These models allow the derivation of pharmacokinetic parameters that can be used to quantify drug distribution and elimination—volume of distribution, clearance, and half-lives. Although the simplicity of compartmental models, compared to physiologic pharmacokinetic models, has its advantages, it also has some disadvantages. For example, cardiac output is not a parameter of compartmental models, and compartmental models therefore cannot be used to predict directly the effect of cardiac failure on drug disposition. The discipline of pharmacokinetics is, to the despair of many, mathematically based. In the succeeding sections, formulas are used to illustrate the concepts needed to understand and interpret pharmacokinetic studies. Pharmacokinetic Concepts The disposition of most drugs follows first-order kinetics. A first-order kinetic process is one in which a constant fraction of the drug is removed during a finite period of time regardless of the drug amount or concentration. Rate constants are usually denoted by the letter k and have units of “inverse time,” such as min −1 or h−1. Because a constant fraction is removed per unit of time in first- order kinetics, the absolute amount of drug removed is proportional to the concentration of the drug. It follows that, in first-order kinetics, the rate of change of the amount of drug at any given time is proportional to the concentration present at that time. First-order kinetics apply not only to elimination, but also to absorption and distribution. Rather than using rate constants, the rapidity of pharmacokinetic processes is often described with half-lives—the time required for the concentration to change by a factor of 2. Half-lives are calculated directly from the corresponding rate constants with this simple equation: 669 Thus, a rate constant of 0. The half-life of any first-order kinetic process, including drug absorption, distribution, and elimination, can be calculated. First-order processes asymptotically approach completion, because a constant fraction of the drug, not an absolute amount, is removed per unit of time. However, after five half-lives, the process will be almost 97% complete (Table 11-4). For practical purposes, this is essentially 100%, and therefore there is a negligible amount of drug remaining in the body. Volume of Distribution The volume of distribution quantifies the extent of drug distribution. The physiologic factor that governs the extent of drug distribution is the overall capacity of tissues versus the capacity of blood for that drug. Overall tissue capacity for uptake of a drug is in turn a function of the total mass of the tissues into which a drug distributes and their average affinity for the drug. In compartmental pharmacokinetic models, drugs are envisaged as distributing into one or more “boxes,” or compartments. Rather, they are hypothetical entities that permit analysis of drug distribution and elimination and description of the drug concentration versus time profile. The volume of distribution is an “apparent” volume because it represents the size of these hypothetical boxes, or compartments, that are necessary to explain the concentration of drug in a reference compartment, usually called the central or plasma compartment. The volume of distribution, V ,d relates the total amount of drug present to the concentration observed in the central compartment: If a drug is extensively distributed, then the concentration will be lower relative to the amount of drug present, which equates to a larger volume of distribution. For example, if a total of 10 mg of drug is present and the concentration is 2 mg/L, then the apparent volume of distribution is 5 L. On the other hand, if the concentration was 4 mg/L, then the volume of distribution would be 2. Simply stated, the apparent volume of distribution is a numeric index of the extent of drug distribution that does not have any relationship to the actual volume of any tissue or group of tissues. It may be as small as plasma volume, or, if overall tissue uptake is extensive, the apparent volume of 670 distribution may greatly exceed the actual total volume of the body. In general, lipophilic drugs have larger volumes of distribution than hydrophilic drugs. Because the volume of distribution is a mathematical construct to model the distribution of a drug in the body, the volume of distribution cannot provide any information regarding the actual tissue concentration in any specific real organ in the body. However, this simple mathematical construct provides a useful summary description of the behavior of the drug in the body. In fact, the loading dose of drug required to achieve a target plasma concentration can be easily calculated by rearranging Equation 11-6 as follows: Table 11-4 Half-lives and Corresponding Percentage of Drug Removed Based on this equation, it is clear that an increase in the volume of distribution means that a larger loading dose will be required to “fill up the box” and achieve the same concentration. Therefore, any change in state because of changes in physiologic and pathologic conditions can alter the volume of distribution, necessitating therapeutic adjustments. Total Drug (Elimination) Clearance Elimination clearance (drug clearance) is the theoretical volume of blood from which drug is completely and irreversibly removed in a unit of time. Total drug clearance can be calculated with pharmacokinetic models of blood concentration versus time data. Drug clearance is often corrected for weight or body surface area, in which case the units are mL/min/kg or mL/min/m ,2 respectively.

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The importance of continuous patient monitoring is discussed—in particular levitra professional 20 mg sale, the response of the patient to commands as a guide to the level of sedation levitra professional 20 mg line. The appropriate monitoring of ventilation discount 20mg levitra professional visa, oxygenation order levitra professional mastercard, and hemodynamics is also discussed, and recommendations are made for the contemporaneous recording of these parameters. The task force strongly suggests that an individual other than the person performing the therapeutic or diagnostic procedure be available to monitor the patient’s comfort and physiologic status. Specific educational objectives include the potentiation of sedative-induced respiratory depression by concomitantly administered opioids, adequate time intervals between doses of sedative/analgesics to avoid cumulative over-dosage, and familiarity with sedative/analgesic antagonists. At least one person with Basic Life Support training should be available during moderate sedation, with immediate availability (1 to 5 minutes) of personnel trained in Advanced Life Support. This individual should have the ability to recognize airway obstruction, establish an airway, and maintain oxygenation and ventilation. The practice guidelines recommend that appropriate patient- size emergency equipment be readily available, specifically including equipment for establishing an airway and delivering positive pressure ventilation with supplemental oxygen, emergency resuscitation drugs, and a working defibrillator. Adequate postprocedure recovery care with appropriate monitoring must be provided until discharge. Controversy exists regarding the level of training required for nonanesthesiologists to be credentialed to provide moderate and deep sedation. These “anesthesia” services must be provided by: A qualified anesthesiologist; a doctor of medicine or osteopathy, a dentist, oral surgeon, or podiatrist who is qualified to administer anesthesia under state law; an appropriately supervised Certified Registered Nurse Anesthetist or Anesthesia Assistant, all who are separate from the practitioner performing the procedure. Failure to follow these recommendations could put patients at increased risk of significant injury or death. These devices integrate patient monitoring variables with the programmed delivery of propofol. The manufacturer of this system required that it should only be used in facilities where an anesthesia professional is immediately available to assist or consult as needed. However, the device worked in conjunction with a single administered dose of fentanyl given 3 minutes prior to the start of a propofol infusion in an attempt to yield some analgesic effect. After a maintenance infusion rate escalation, further increases were limited by a 3-minute lockout period. There were several safety mechanisms in place to ensure both adequate depth of sedation, and prevention of oversedation. An automated responsiveness monitor actuated by the patient assessed his/her responsiveness by requiring interaction with a hand-held device when prompted by vibratory or auditory stimulation. Oxygen delivery was also automatically titrated as determined by oxygen saturation measurement. There were alarm systems to alert the provider to low respiratory rate, low oxygen saturation or apnea events. Monitored anesthesia care presents an opportunity for our patients to observe us at work. For the anesthesiologist, monitored anesthesia care presents an opportunity to provide a more prolonged and intimate level of care and reassurance to our patients that is in contrast to the more limited exposure that occurs during and after general anesthesia. Our airway management skills and our daily practice of applied pharmacology make us uniquely qualified to provide this service. Monitored anesthesia care presents us with an opportunity to display these skills and increase our recognition in areas outside the operating room. The availability of drugs with a more favorable pharmacologic profile allows us to tailor our techniques to provide the specific components of analgesia, sedation, anxiolysis, and amnesia with minimal morbidity and to facilitate a prompt recovery. As the population ages, increasing numbers of patients will become candidates for monitored anesthesia care. It is our responsibility to clearly demonstrate to our nonanesthesia colleagues that anesthesiologist-provided monitored anesthesia care contributes to the best outcome for our patients. If anesthesiologists are not willing or able to provide these services, others, who are less well qualified, are prepared to assume that role. The effect of the assignment of a pre-sedation target level on procedural sedation using propofol. Comparison of a computer-assisted infusion versus intermittent bolus administration of alfentanil as a supplement to nitrous oxide for lower abdominal surgery. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Context-sensitive half-times: What are they and how valuable are they in anaesthesiology? Use of alfentanil and propofol for outpatient monitored anesthesia care: Determining the optimal dosing regimen. Pharmacokinetic- pharmacodynamic modeling of the electroencephalographic effects of benzodiazepines. Comparison of propofol administration techniques for sedation during monitored anesthesia care. The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. Reduction by fentanyl of the Cp50 values of propofol and hemodynamic responses to various noxious stimuli. The pharmacodynamic interaction between propofol and fentanyl with respect to the suppression of somatic or hemodynamic responses to skin incision, peritoneum incision, and abdominal wall retraction. Hypnotic and anaesthetic interactions between 2088 midazolam, propofol and alfentanil. Achieving control of anesthetic administration: The infusion pump versus the vaporizer. Fentanyl or alfentanil decreases the minimum alveolar anesthetic concentration of isoflurane in surgical patients. Anesthesia matters: Patients anesthetized with propofol have less postoperative pain than those anesthetized with isoflurane. A comparison of propofol and midazolam by infusion to provide sedation in patients who receive spinal anaesthesia. Sedative infusions during local and regional anesthesia: a comparison of midazolam and propofol. Propofol decreases early postoperative nausea and vomiting in patients undergoing thyroid and parathyroid operations. Day-surgery patients anesthetized with propofol have less postoperative pain than those anesthetized with sevoflurane. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. Propofol anaesthesia and postoperative nausea and vomiting: Quantitative systematic review of randomized controlled studies. Comparison of propofol, droperidol, and metoclopramide for prophylaxis of postoperative nausea and vomiting after breast cancer surgery: A prospective, randomized, double-blind, placebo-controlled study in Japanese patients. Prevention of postoperative nausea and vomiting with a small dose of propofol combined with dexamethasone 4 mg or dexamethasone 8 mg in patients undergoing middle ear surgery: a prospective, randomized, double- blind study. Fospropofol disodium injection for the sedation of patients undergoing colonoscopy. Erroneously published fospropofol pharmacokinetic-pharmacodynamic data and retraction of the affected publications. Fospropofol assay issues and impact on pharmacokinetic and pharmacodynamic evaluation. Fospropofol assay issues and impact on pharmacokinetic and pharmacodynamic evaluation. Clinical trial: A dose-response study of fospropofol disodium for moderate sedation during colonoscopy. A randomized, double-blind, phase 3 study of fospropofol disodium for sedation during colonoscopy. Propofol versus midazolam for monitored sedation: A comparison of intraoperative and recovery parameters. Propofol and alfentanil for sedation during placement of retrobulbar block for cataract surgery. Effects of fentanyl on pain and hemodynamic response after retrobulbar block in patients having phacoemulsification. A comparison of midazolam, alfentanil and propofol for sedation in outpatient intraocular surgery.