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By Y. Bozep. Christopher Newport University.

J Thorac Cardiovasc cyte filters in reducing tumor cell contamination after intra- Surg 2001; 122: 1041−1042 purchase januvia 100mg online blood sugar 150. Artif Organs 1997; 21: osteosarcoma cells with intraoperative “mesh autotransfu- 763−765 purchase januvia 100mg with mastercard diabetes medications while breastfeeding. Ann Thorac Surg dence of tumour cell removal from salvaged blood after 2005; 79: 234−240. The proposed changes, and are largely a result of interruption of cerebral mechanism for ’glutamate excitotoxicity’ involves acti- blood flow during arch surgery. Intracerebral levels of the excitatory amino acid Understanding the pathophysiologic mechanisms of glutamate were quantitatively measured using a micro- neurological injury is the key to improved patient out- dialysis technique. The hypoxic/ischemic insult, which results from ischemic insult, in the form of circulatory arrest, results in the interruption of cerebral blood flow, sets into motion an elevation of intracerebral glutamate which persists for a complex cascade of events which ultimately leads to up to 20 hours [3]. The animals were recovered afer the ischemic insult of key steps in this pathway can prevent the accumulation and were sacrificed afer three days. They were assessed of toxic metabolites, which can potentially mitigate neuro- for functional neurological recovery, as well as histopatho- logical sequelae. Although this remains an active area of logic evidence of neuronal injury afer brain harvesting at investigation within cardiac surgery, there are currently no 72 hours. Histologically, control animals displayed a sig- available agents that directly block neurological injury. Canine superoxide anion to form peroxynitrite, a potent oxi- animals were given a simultaneous infusion of artificial dant. Neuronal drial disruption causes a release of cytochrome c, which necrosis appears to increase with time up to 72 hours; in turn can activate caspase enzymes. The caspases then however, apoptosis peaks at approximately 8 hours afer injury and begins to disappear by 72 hours. In a recent study of hypoxic enceph- of the molecular mechanisms of these apoptotic pathways alopathy in neonatal rats, unilateral carotid ligation was becomes exceedingly complex. However, this remains the used at varying time points prior to global ischemia to key to finding new neuroprotective therapeutic targets. Lee and colleagues also membrane and thus uncouple oxidative phosphorylation demonstrated that these pharmacologic agents adminis- from respiration. It is believed to decrease free radical produc- tions as a result of aortic surgery. Further investigations tion, while at the same time promoting mitochondrial are likely to reveal transcription factors, in addition to proliferation in the cell. Mitochondrial potassium fluxes can affect cytochrome c release and caspase activa- Ischemic preconditioning is a paradoxical form of protec- tion which can adversely affect neuronal survival via the tion against lethal ischemia by exposure to brief episodes apoptotic mechanisms described previously [15]. Although initially described in cardiac myocytes, a similar mechanism was also found in neurons [23]. The molecular mechanisms Altered gene expression of ischemic preconditioning are incompletely under- As we continue to uncover the molecular mechanisms of stood. This only further substantiated the subtle expression profiling is necessary in larger animal models nature of the injury patern, which is believed to occur in order to identify potential neuroprotective genes and at a subcellular, mitochondrial level. In fact, in and apoptosis in the diazoxide-pretreated animals [27] those dogs pretreated with glybenclamide, the functional (Figure 33. Glutamate excito- sodium extrusion and intracellular calcium accumula- toxicity: a mechanism of neurologic injury associated with cir- tion. Neuronal nitric oxide syn- of circulatory arrest, as compared with a control group thase inhibition reduces neuronal apoptosis after hypother- receiving no drug pretreatment [30]. Glutamate mediates cell death and increases the Bax to Bcl-2 ratio in a differentiated patients. Uncoupling the general cardiac surgery population, especially when protein-2 prevents neuronal death and diminishes brain circulatory arrest becomes necessary. Nat Med 2003; ous surgical strategies and intra-operative monitoring 9: 1062–1068. Mitochondrial uncou- However, the key to reducing and preventing neurologi- pling protein 2 in the central nervous system: neuromod- cal sequelae is understanding the pathophysiologic mech- ulator and neuroprotector. Mitochondrial potassium channels and intervention at various points in the injury cycle. Various uncoupling proteins in synaptic plasticity and neuronal cell animal models of neuronal injury have demonstrated the death. Neuron 2002; directly block neurological injury, continued investiga- 35: 605–623. Novel roles for arginase in cell survival, regeneration, and translation in the central nervous 1. Neurologic injury after cardiopulmonary the nuclear control of mitochondrial function in mammalian bypass surgery. Stroke Na+-H+ exchange inhibition prior to 90 minutes of hypother- 2003; 34: 1796–1802. Introduction Although aortic arch surgery is still extremely challenging, recent technical advances have greatly reduced such risks Despite remarkable recent improvements in surgical during the operation [5,6]. More prolonged neurological dysfunction may literature shows that, although there are many reports of accompany coma from metabolic or ischemic encepha- surgical improvements, analyses of the morbidity and mor- lopathy, quadriparesis caused by acquired critical illness tality resulting from neurological complications afer aortic polyneuromyopathy, and cognitive deficits. Furthermore, data regarding neurological deficits can result from perioperative stroke long-term outcome, including survival, functional status, or cerebral hemorrhage, post-anoxic encephalopathy, quality of life, and healthcare costs are very scarce. This chapter will discuss the evaluation and management of patients with these neurological compli- Transient neurological complications cations associated with aortic arch surgery. The first signs of a possible neurological complication afer aortic arch surgery are ofen delayed emergence Risk factors for neurological from anesthesia and extubation, and excessive restless- complications ness and agitation. The patient should undergo a care- ful neurological examination to assess for deficits before Pre-operative risks factors for neurological complications sedation is arbitrarily given. Any suspected new focal include older age, severity of aneurysm or dissection neurological impairment should trigger a neurological symptoms, advanced atherosclerotic disease, and other consultation for further evaluation. Therefore, if possible, these medical conditions need to be corrected or stabi- Delirium lized before surgery [1,3]. Intra-operative risk factors for neurological complica- Perioperative delirium (or acute confusional state) tions include the urgency of the surgery, the complexity occurs most frequently in elderly patients and in patients of the arch repair, circulatory arrest time, cardiopulmo- who have undergone major surgery [4]. It is character- nary bypass time, inadequate cerebral perfusion, blood ized by confusion, agitation, disorientation, fluctuating Aortic Arch Surgery: Principles, Strategies and Outcomes. However, the patient typically is able to move their tremor, myoclonus, and seizure. The cause is an excessive limbs spontaneously without notable weakness or restric- amount of serotonin precursors or agonists, combined tion. These symptoms may be triggered by a variety of with monoamine oxidase inhibitors. Therefore, cli- common causes are medication effects, pain and discom- nicians should be aware of the common post-operative fort, hypoxemia or hypercapnia, metabolic derangement, drug-induced and drug withdrawal syndromes so as to sleep disturbance, and withdrawal from alcohol or seda- avoid sudden discontinuation of certain medications and tives. Pharmacological agents are important contributors to to quickly initiate appropriate symptomatic treatments. Medications associated with delir- Strategies to prevent or reduce perioperative delir- ium include anticholinergic drugs, anesthetics, opioids, ium should include close monitoring and correction of antihistamines, benzodiazepines, cardiovascular agents, hypoxemia, hypotension, fluid and electrolyte imbalance, and antimicrobials [9]. Therefore, unsuita- tors for worsening delirium that should be considered ble and unnecessary medications should be avoided post- include: the patient’s cognitive impairment, sleep depriva- operatively.

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Consider the situation in which most information about diagnostic tests is obtained cheap januvia online mastercard diabetes diet in nigeria. Under these circumstances order januvia 100mg overnight delivery diabetes type 2 urine test, physicians are using the test in the process of caring for patients. They feel justified in proceeding with more exhaustive evaluation, in the patient’s best interest, only when preliminary diagnostic tests are positive. They are naturally reluctant to initiate an aggressive workup, with its associated risks and expenses, when the test is negative. As a result, information on negative tests, whether true negative or false negative, tends to be much less complete in the medical literature. The researchers understandably were reluctant to subject men to an uncomfortable procedure without supporting evidence. The clinical manifestations were described nearly a century ago, yet there is still no better way to substantiate the presence of angina pectoris than a carefully taken history. Certainly, a great many objectively measurable phenomena are related to this clinical syndrome, for example, the presence of coronary artery stenosis seen on angiography, delayed perfusion on a thallium stress test, and characteristic abnormalities on electrocardiograms both at rest and with exercise. But none is so closely tied to the clinical syndrome that it could serve as the standard by which the condition is considered present or absent. The validity of a laboratory test is established by comparing its result to a clinical diagnosis based on a careful history of symptoms and a physical examination. Once established, the test is then used to validate the clinical diagnosis gained from history and physical examination. An example would be the use of manometry to ‘confirm’ irritable bowel syndrome, because the contraction pattern demonstrated by manometry and believed to be the characteristic of irritable bowel syndrome was validated by clinical impression in the first place. They must choose as their standard of validity another test that admittedly is imperfect but is considered the best available. Just such a situation occurred in a comparison of real-time ultrasonography and oral cholecystography for the detection of gallstones. In five patients, ultrasound was positive for stones that were missed on cholecystography. Two of the patients later underwent surgery and gallstones were found, so that for at least those two patients, the standard oral cholecystogram was actually less accurate than the newer real-time ultrasound. Similarly, if the new test is more often negative in patients who really do not have the disease, results for those patients will be considered false negatives compared with the old test. Thus, if an inaccurate standard of validity is used, a new test can perform no better than that standard and will seem inferior when it approximates the truth more closely. A simple way of looking at the relationships between the test results and the true diagnosis (by Gold Standard) is shown in Table. The test is considered to be either positive (abnormal) or negative (normal) and the disease either present or absent. There are then four possible interpretations of test result, two of which are correct, and two wrong. Thus when a gold standard is available, the categorization of test results into ‘true positives’ (disease present by both the tests), ‘false positives’ (disease present only by the test but not by the gold standard), ‘true negatives’ (disease absent by both the tests) and ‘false negatives’ (disease absent by the test but present by the gold standard) is best done by constructing a 2 × 2 table (Table 7. From the table the following statistical parameters of diagnostic accuracy can be calculated: 1. However, there are several other criteria, which need to be taken into consideration while choosing optimal sensitivity of a test. Positive a = 27 b = 35 a + b = 62 Negative c = 10 d = 77 c + d = 87 Total a + c = 37 b + d = 112 a + b + c + d = 149 positive” result. In other words, 31 percent of non-diseased people screened by the test (clinical diagnosis) will be wrongly classified as “diseased” when they are not. Use Specific tests are useful to confirm (or “rule in”) a diagnosis that has been suggested by other data. This is because a highly specific test is rarely positive in the absence of disease—that is, it gives few false positive results. For diseases like diabetes for which treatment does not markedly alter outcome, specificity must be high and early cases may be missed, but false positives should be limited; otherwise the health system will be overburdened with diagnostic demands on the positives, both true and false. Highly specific tests are particularly needed when false positive result can harm the patient physically, or financially. Thus before patients are subjected to cancer chemotherapy, with all its attendant risks, emotional trauma, and financial costs, tissue diagnosis is generally required instead of relying upon less specific tests. That is, high specificity is necessary when false positive errors must be avoided. Bias Sometimes the sensitivity and specificity of a test are not established independently of the means by which the true diagnosis is established leading to biased assessment of the test’s properties. As already mentioned, if the test is evaluated using data obtained during the course of a clinical evaluation of patients suspected of having the disease in question, a positive test may prompt the clinician to continue pursuing the diagnosis, increasing the likelihood that the disease will be found. On the other hand, a negative test may cause the clinician to abandon further testing making it more likely that the disease if present will be missed. In other situations, the test result may be part of the information used to establish the diagnosis or conversely, the results of the test may be interpreted taking other clinical information of the final diagnosis into Research on Diagnostic Tests 75 account. Because X-ray interpretation is somewhat subjective, it is easy to be influenced by the clinical information provided. All clinicians experience the situation of having X-rays over read because of a clinical impression, or conversely, of going back over old-X-ray in which a finding was missed because a clinical event was not known at the time and therefore attention was not directed to the particular area in the X-ray. Because of these biases, some radiologists prefer to read X-rays twice, first without and then with the clinical information. All of these biases tend to increase the agreement between the test and the standard of validity. Chance Values for sensitivity and specificity (or likelihood ratios and other characteristics of diagnostic test discussed later in this chapter) are usually estimated from observations on relatively small sample of people with and without the disease of interest. Because of chance (random variation) in any one sample, particularly if it is small, the true sensitivity and specificity of the test can be misrepresented, even if there is no bias in the study. The particular values observed are compatible with a range of true values, typically characterized by the ‘95% confidence interval’. The width of this range of values defines the degree of precision of the estimates of sensitivity and specificity. Therefore, reported values for sensitivity and specificity should not be taken too literally if a small number of patients are studied. The 95% confidence interval of a proportion is easily estimated by the following formula based on the binomial theorem: p = 1. The precision of estimates of sensitivity increases as the number of people on which the estimate is based increases. False Negatives and False Positives Whereas the epidemiologist thinks in terms of sensitivity, the clinician thinks in terms of false negatives and false positives. However, laboratory physician has to think in terms of both the characteristics, i. False Negative Rate: The term “false negative” means that patients who actually have the disease (Gold standard positive) are told that they do not have the disease (Test result negative). The sensitivity of a test (clinical diagnosis) is 73 percent and false negative rate is 27 percent.

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These principles notwithstanding buy januvia 100 mg overnight delivery metabolic disease pdf, the location of the embolic source does not always precisely correspond A thorough history and physical examination can estab- with the anterior vs buy januvia with paypal diabetes type 1 quality of life. Because of the high auscultation of the upper anterior chest and neck will pro- prevalence of coronary artery disease in patients who vide much information in patients with aortic arch dis- harbor lesions of the aortic arch vessels, pre-operative ease. Bluish discoloration of the digits, subungual splinter assessment must include functional non-invasive cardiac hemorrhages, livedo reticularis or frank tissue loss associ- evaluation. We obtain a sestamibi scan or a dobutamine ated with weak or absent pulses, thrills and bruits over stress echocardiogram routinely. If transthoracic repair is the neck and chest can be diagnostic for atherosclerotic contemplated, one should have a low threshold for obtain- disease in the aortic arch vessels. Blood pressure measure- ing a coronary angiogram, to identify surgically correct- ments in both upper limbs and, in patients with suspected able coronary artery disease prior to median sternotomy. A difference in blood pressure between the two arms will support subclavian or innominate artery disease. Indications for surgical repair Duplex ultrasonography is a first-line diagnostic tool for the assessment of aortic arch vessel disease. Although In general, the main indications for surgical repair of the the intrathoracic portions of the arch vessels are not visu- aortic arch vessels are symptoms in the cerebral or upper alized with duplex scanning, the study provides indirect extremity circulation, provided that they can be related evidence of arch vessel involvement: dampened arterial to one of the aortic arch vessel lesions. The second portion of the subclavian artery There is not enough evidence to support routine repair is well seen with ultrasound, but the first and third por- of asymptomatic occlusion of the common carotid or the tions may be obscured by the clavicle and the ribs. A of silent cerebral infarcts lends support to endovascular difference of 6 mmHg between the two eyes or an oculo- or open surgical repair in good risk patients. Multiplane catheter aor- subclavian artery does not warrant repair, as the rich tography with selective catheterization of the aortic arch collateral supply of the head, neck and shoulder provides vessels also allows for cerebral and upper extremity sufficient perfusion to the vertebral and upper extrem- run-off views, if needed. In asymptomatic patients, radiological study for evaluating the arch vessels [35]. A combination of multiple imaging modalities, sis, then either the carotid lesion is addressed first or including carotid duplex scanning, may be needed in the patient can have a combined carotid endarterectomy some patients to fully assess the arch and cerebral arterial and subclavian reconstruction with subclavian reim- anatomy. Revascularization of the aortic artery stenosis following coronary revascularization arch vessels, in particular if the disease involves multiple with the ipsilateral internal thoracic artery may develop branches, is associated with reperfusion hyperemia. Subclavian revascularization with Increased blood flow to the peri-infarct area can be det- stent or carotid-subclavian bypass in these patients is rimental due to the loss of vascular autoregulation in justified. Therefore, it is usually prudent to delay inter- grade subclavian artery stenosis in preparation for ventions at least by 4–6 weeks afer a major cerebral inf- coronary artery revascularization using the internal arct to reduce the chance of post-operative neurological thoracic artery may also be justified. In recent years, endovascular techniques with angio- Transthoracic approach plasty and stents have been used with increasing frequency for repair of aortic arch vessel lesions [17−22]. If revascu- Pre-operative preparation larization is indicated, but the endovascular procedure carries high risk of cerebral or upper extremity emboliza- Intra-operative monitoring of blood pressure with upper tion, open surgical repair should be performed. There are extremity arterial lines or cuffs is ofen not feasible in two major surgical approaches for repair of aortic arch ves- patients who need arch vessel reconstruction; therefore, sel occlusive disease: transthoracic and cervical. Whenever it may be necessary to use a femoral arterial line for con- appropriate, the cervical approach is favored because of the tinuously monitoring the patient’s blood pressure. However, a transtho- lef jugular and subclavian veins have to be avoided for racic approach is the primary choice for repair of innomi- central venous access sites as mobilization or, rarely, liga- nate artery occlusive disease or for extensive disease of the tion of the lef brachiocephalic vein may be required for aortic arch vessels when more than one large vessel requires adequate exposure. Additionally, transthoracic repair dure, the surgeon should communicate these concerns to can be performed if thoracotomy is done for another con- the anesthesiology team in advance. Relative contraindications for transthoracic repair are previous sternotomy, poor cardiac or pulmonary condition, limited life expectancy Exposure of the aortic arch vessels using and advanced age. In case of extensive aortic arch vessel median sternotomy occlusive disease, there is some controversy regarding the The trunk of all aortic arch vessels can be exposed from optimal extent of trans-sternal repair. Berguer and Kieffer a median sternotomy; however, the posterior position of usually recommend the more extensive reconstruction the lef subclavian artery makes its exposure cumbersome whenever possible, including bypass to the lef subcla- from this approach. The reason for this philosophy is the be extended into the neck along the medial edge of the presumption that the lef subclavian artery can be used as right sternocleidomastoid muscle to provide exposure to an inflow for cervical bypass in the future if one or more the distal innominate, the right subclavian and common of the other grafs occlude. In general, the cervical upper sternotomy is an excellent exposure of the innomi- approach is used for isolated common carotid or sub- nate artery and should be considered if the ascending clavian disease or in any other patients who are unsuit- aorta does not need cross-clamping. The decision ascending aorto-innominate artery bypass is performed between transthoracic versus transcervical approaches is through a complete median sternotomy [9,14]. Berguer mainly determined by the expected and desired safety as performs this operation through a partial sternotomy well as the durability of the repair. If venously and the right common carotid, subclavian and the division is done, mild and usually just transient symp- innominate arteries are cross-clamped, in this sequence, toms of venous congestion in the lef upper extremity to minimize the risk of embolization. The innominate artery is situated posterior to normal proximal innominate artery, it can be occluded the lef brachiocephalic vein. Otherwise, it maybe is dissected more distally towards the carotid-subcla- necessary to partially occlude the aortic arch, which can vian bifurcation. It is dependent on the surgeon’s experience to judge if the To have a comfortable segment for the proximal inflow aorta is sof enough for partial clamping. The endarterectomy is developed cir- Innominate artery endarterectomy cumferentially in the middle of the media to ensure that Innominate artery endarterectomy is indicated only in the remaining arterial wall maintains enough strength. Distally, the endarterectomy plane is tapered to extends beyond the origin of the right common carotid obtain an appropriate end point; tacking sutures may or subclavian arteries, it may be difficult to obtain a satis- be used as necessary. In patients with primarily with 5-0 monofilament sutures, or using a syn- Takayasu’s or radiation arteritis, it is usually impossible thetic patch. The tomy, since simultaneous occlusion of flow to both carotid subcutaneous layer and skin are closed with absorbable circulations should be avoided. While Ascending aorta to innominate artery bypass Berguer advocates placing the graf anterior to the lef Following appropriate exposure of the aortic arch vessels, innominate vein, we position the graf under the vein using complete or partial sternotomy, the pericardium to avoid compression of the vein by the graf (Figures is opened and tented with stay sutures and the ascend- 30. The bypass has to run as lateral to to place the ascending aortic graf in the lateral posi- the aorta as possible, because a graf anterior to the aorta tion, tunneling the graf under the lef innominate vein carries the risk of being compressed by the sternum or is quite easy. If the ‘single trunk’ technique is used, it it can be the source of life-threatening bleeding if re-do may be helpful to sew the side arm to the main trunk sternotomy is required. If more than one vessel is to be before making the proximal anastomosis (Figures 30. We prefer the later, as it makes the bypass tomosis is performed, to beter assess the position of the less bulky. Adding the side arm afer a concern, since undue compression on the vessels and completion of the first bypass is also possible, although the trachea can lead to graf occlusion, superior vena cross-clamping of the graf may result in prolonged cava syndrome or airway compromise. A portion of the artery has been removed and the proximal stump oversewn with pledgeted sutures. The innominate artery may be completely transected and the distal anastomosis is fashioned end-to-end to the dis- tal innominate artery (Figures 30. For the anatomoses, 5-0 or, occasionally, 6-0 monofilament sutures are used with carefully planned bites. The proximal innominate artery is oversewn with 5-0 or 4-0 monofilament sutures, rein- forced with felt pledgets. Transthoracic grafing of the innominate artery is not infrequently performed in conjunction with revasculari- zation of the lef common carotid, or, occasionally, the lef subclavian artery. Monofilament sutures (3-0 or 4-0) are used for the It is important to relax the sternal retractor before proximal anastomosis with large bites into the aorta. The proximal anastomosis is tested and the patient is In patients with bilateral common carotid reconstruction, then fully heparinized. The innominate, right subcla- we revascularize the occluded side first to decrease the vian and right common carotid arteries are clamped, risk of cerebral ischemia and provide contralateral collat- then the innominate artery is opened longitudinally.

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