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Drug distribution within the central compartment is considered to be instantaneous kamagra polo 100mg. However 100 mg kamagra polo, drug uptake into some of the highly perfused tissues is so rapid that it cannot be detected as a discrete phase on the plasma concentration versus time curve kamagra polo 100 mg. The distribution and elimination phases can be characterized by graphic 676 analysis of the plasma concentration versus time curve 100mg kamagra polo, as shown in Figure 11-6 . The elimination phase line is extrapolated back to time zero (the time of injection) . In Figure 11-6 , the zero time intercepts of the distribution and elimination lines are points A and B , respectively . The hybrid rate constants , α and β, are equal to the slopes of the two lines, and are used to calculate the distribution and elimination half-lives; α and β are called hybrid rate constants because they depend on both distribution and elimination processes. The first term characterizes the distribution phase and the second term characterizes the elimination phase. Immediately after injection, the first term represents a much larger fraction of the total plasma concentration than the second term. After several distribution half- lives, the value of the first term approaches zero, and the plasma concentration is essentially equal to the value of the second term (Fig. In multicompartmental models, the drug is initially distributed only within the central compartment. Therefore, the initial apparent volume of distribution is the volume of the central compartment. Immediately after injection, the amount of drug present is the dose, and the concentration is the extrapolated concentration at time t = 0, which is equal to the sum of the intercepts of the distribution and elimination lines. If doses are not correspondingly reduced, the higher plasma concentrations will increase the incidence of adverse pharmacologic effects. Drug moves from the central to the peripheral compartment, which also has a volume, V2. This intercompartmental transfer is a first-order process, and its magnitude is quantified by the rate constant k12. As soon as drug appears in the peripheral compartment, some passes back to the central compartment, a process characterized by the rate constant k21. The transfer of drug between the central and peripheral compartments is quantified by the distributional or intercompartmental clearance: The third process that begins immediately after administration of the drug is irreversible removal of drug from the system via the central compartment. At equilibrium, the drug is distributed between the central and the peripheral compartments, and by definition, the drug concentrations in the compartments are equal. Therefore, the ultimate volume of distribution, termed the volume of distribution at steady-state (Vss), is the sum of V1 and V2. Extensive tissue uptake of a drug is reflected by a large volume of the peripheral compartment, which, in turn, results in a large Vss. As in the single-compartment model, in multicompartment models the elimination clearance is equal to the dose divided by the area under the concentration versus time curve. This area, as well as the compartmental volumes and intercompartmental clearances, can be calculated from the intercepts and hybrid rate constants, without having to reach steady-state 678 conditions. Therefore, the plasma concentration is the sum of three exponential terms: where t = time, Cp(t) = plasma concentration at time t, A = intercept of the rapid distribution phase line, α = hybrid rate constant of the rapid distribution phase, B = intercept of the slower distribution phase line, β = hybrid rate constant of the slower distribution phase, G = intercept of the elimination phase line, and γ = hybrid rate constant of the elimination phase. This triphasic behavior is explained by a three-compartment pharmacokinetic model (Fig. As in the two-compartment model, the drug is injected into and eliminated from the central compartment. Drug is reversibly transferred between the central compartment and two peripheral compartments, which accounts for two distribution phases. Drug transfer between the central compartment and the more rapidly equilibrating, or “shallow,” peripheral compartment is characterized by the first-order rate constants k12 and k21. Transfer in and out of the more slowly equilibrating, “deep” compartment is characterized by the rate constants k13 and k31. In this model, there are three compartmental volumes: V , V ,1 2 and V ,3 whose sum equals Vss; and three clearances: the rapid intercompartmental clearance, the slow intercompartmental clearance, and elimination clearance. The pharmacokinetic parameters of interest to clinicians, such as clearance, volumes of distribution, and distribution and elimination half-lives, are determined by calculations analogous to those used in the two- compartment model. Accurate estimates of these parameters depend on accurate characterization of the measured plasma concentration versus time data. A frequently encountered problem is that the duration of sampling is not long enough to define accurately the elimination phase. Conversely, samples are sometimes obtained too infrequently following drug administration to be able to characterize the distribution phases accurately. In fact, some drugs have two-compartment10 kinetics in some patients and three-compartment kinetics in others. In selecting a pharmacokinetic model, the most important factor is that it accurately characterizes the measured concentrations. In general, the model with the smallest number of compartments or exponents that accurately reflects the data is used. However, it is good to consider that the data collected in a particular study may not be reflective of the clinical pharmacologic issues of concern in another situation, making published pharmacokinetic model parameters potentially irrelevant. In this case, the pharmacokinetic models will not be of use in designing dosing regimens for drug X that avoid toxic drug concentrations at 1 minute. With this technique, pharmacokinetic parameters were estimated independently for each subject and then averaged to provide estimates of the typical parameters for the population. One problem with this approach is that if outliers are present, averaging parameters could result in a model that does not accurately predict typical drug concentrations. Currently, most pharmacokinetic models are developed using population pharmacokinetic modeling, which has been made feasible because of advances in modeling software and increased computing power. With these techniques, the pharmacokinetic parameters are estimated using all the concentration versus time data from the entire group of subjects in a single stage, using sophisticated nonlinear regression methods. This modeling technique provides single estimates of the typical parameter values for the population. Noncompartmental (Stochastic) Pharmacokinetic Models Often investigators performing pharmacokinetic analyses of drugs want to avoid the experimental requirements of a physiologic model—data or empirical estimations of individual organ inflow and outflow concentration profiles and organ tissue drug concentrations are required in order to identify 680 the components of the model. Although compartmental models do not40 assume any physiologic or anatomic basis for the model structure, investigators often attribute anatomic and physiologic function to these empiric models. Even if the disciplined clinical pharmacologist avoids41 overinterpretation of the meaning of compartment models, the simple fact that several competing models can provide equally good descriptions of the mathematical data, or that some subjects in a data set may better fit with a three-compartment model rather than the two-compartment model that provides the best fit for the other data set subjects, leads many to question whether there is a true best model architecture for any given drug. Therefore, some investigators choose to employ mathematical techniques to characterize a pharmacokinetic data set that attempt to avoid any preconceived notion of structure, and yet yield the pharmacokinetic parameters that summarize drug distribution and elimination. These techniques are classified as noncompartmental techniques or stochastic techniques and are similar to the methods based on moment analysis utilized in process analysis of chemical engineering systems. Although these techniques are often called model- independent, like any mathematical construct, assumptions must be made to simplify the mathematics. The basic assumptions of noncompartmental analysis are that all of the elimination clearance occurs directly from the plasma, the distribution and elimination of drug is a linear and first-order process, and the pharmacokinetics of the system does not vary over the time of the data collection (time-invariant). All of these assumptions are also made in the basic compartmental, and most physiologic, models. Therefore, the main advantage of the noncompartmental pharmacokinetic methods is that a general description of drug absorption, distribution, and elimination can be made without resorting to more complex mathematical modeling techniques. In fact, when properly defined, the estimates of these parameters from the noncompartmental approach and a well-defined compartmental model yield similar values. However, the premise behind developing models to better characterize and understand the effects of various physiologic and pathologic states on drug distribution and elimination was that the relationship between a dose of drug and its effect(s) had already been characterized. As computational power and drug assay technology grew, it became possible to characterize the relationship between a drug concentration and the associated pharmacologic effect. As a result, pharmacodynamic studies since the nineties have focused on the quantitative analysis of the relationship between the drug concentration in the blood and the resultant effects of the drug on physiologic processes. Drug–Receptor Interactions Most pharmacologic agents produce their physiologic effects by binding to a drug specific receptor, which brings about a change in cellular function. The majority of pharmacologic receptors are cell membrane bound proteins, although some receptors are located in the cytoplasm or the nucleoplasm of the cell. Binding of drugs to receptors, like the binding of drugs to plasma proteins, is usually reversible, and follows the Law of Mass Action: This relationship demonstrates that the higher the concentration of free drug or unoccupied receptor, the greater the tendency to form the drug– receptor complex. Plotting the percentage of receptors occupied by a drug against the logarithm of the concentration of the drug yields a sigmoid curve, as shown in Figure 11-9. In the left panel, the response data is plotted against the dose data on a linear scale. In the right panel, the same response data are plotted against the dose data on a logarithmic scale yielding a sigmoid dose–response curve that is linear between 20% and 80% of the maximal effect. The percentage of receptors occupied by a drug is not equivalent to the percentage of maximal effect produced by the drug. In fact, most receptor systems have more receptors than required to obtain the maximum drug effect. The presence of “extra” unoccupied receptors will promote the45 formation of the drug–receptor complex (Law of Mass Action, Equation 11- 17); therefore, near-maximal drug effects can occur at very low drug concentrations. This not only allows extremely efficient responses to drugs, but it provides a large margin of safety—an extremely large number of a drug’s receptors must be bound to an antagonist before the drug is unable to produce its pharmacologic effect. For example, at the neuromuscular junction, only 20% to 25% of the postjunctional nicotinic cholinergic receptors need to bind acetylcholine to produce contraction of all the fibers in the muscle, while 75% of the receptors must be blocked by a nondepolarizing neuromuscular antagonist to produce a significant drop in muscle strength. There are two primary schemes by which the binding of an agonist to a receptor changes cellular function: receptor-linked membrane ion channels called ionophores, and guanine nucleotide binding proteins, referred to as G-proteins. The nicotinic cholinergic receptor in the neuromuscular postsynaptic membrane is one example of a receptor–ionophore complex. Binding of acetylcholine opens the cation ionophore, leading to an influx of Na ions,+ propagation of an action potential, and, ultimately, muscle contraction. Desensitization and Downregulation of Receptors Receptors are not static entities. Prolonged exposure of a receptor to its agonist leads to desensitization—subsequent doses of the agonist will produce lower maximal effects. With sustained elevation of the cytosolic second messengers downstream of the G-proteins, pathways to prevent further G-protein signaling are activated. Phosphorylation by G- protein receptor kinases and arrestin-mediated blockage of the coupling site needed to form the active heterotrimeric G protein complex prevents G protein coupled receptors from becoming active. Arrestins and other cell membrane proteins can tag receptors that have sustained activity, so that these non–G-protein receptors are internalized and sequestered so they are no longer accessible to agonists. Similar mechanisms will prevent the trafficking of stored receptors to the cell membrane. The combined increased rate of internalization and decreased rate of replenishing of receptor results in downregulation—a decrease in the total number of receptors. Signals that produce downregulation with sustained receptor activation are essentially reversed in the face of constant receptor inactivity. Therefore, chronically denervated neuromuscular junctions, just like cardiac tissue constantly bathed with adrenergic antagonists, will upregulate the specific receptors in an attempt to produce a signal in the face of lower concentrations of agonists. Agonists, Partial Agonists, and Antagonists Drugs that bind to receptors and produce an effect are called agonists. Different drugs that act on the same receptor may be capable of producing the same maximal effect (Emax), although they may differ in the concentration that produces the effect (i. Agonists that differ in potency but bind to the same receptors will have parallel concentration–response curves (Fig. Differences in potency of agonists reflect differences in affinity for the receptor. Partial agonists are drugs that are not capable of producing the maximal effect, even at very high concentrations (Fig. Compounds that bind to receptors without producing any changes in cellular function are referred to as antagonists— antagonists make it 684 impossible for agonists to bind their receptors. Competitive antagonists bind reversibly to receptors, and their blocking effect can be overcome by high concentrations of an agonist (i. Therefore, competitive antagonists produce a parallel shift in the dose–response curve, but the maximum effect is not altered (Fig. This has the same effect as reducing the number of receptors and shifts the dose–response curve downward and to the right, decreasing both the slope and the maximum effect (Fig. The effect of noncompetitive antagonists is reversed only by synthesis of new receptor molecules. Figure 11-10 Schematic pharmacodynamic curves, with dose or concentration on the x- axis and effect or receptor occupancy on the y-axis, that illustrate agonism, partial agonism, and antagonism. Drug A produces a maximum effect, Emax, and a 50% of maximal effect at dose or concentration E50,A. Drug B, a full agonist, can produce the maximum effect, Emax; however, it is less potent (E50,B > E50,A). Drug C, a partial agonist, can only produce a maximum effect of approximately 50% Emax. If a competitive antagonist is given to a patient, the dose response for the agonist would shift from curve A to curve B—although the receptors would have the same affinity for the agonist, the presence of the competitor would necessitate an increase in agonist in order to produce an effect. In fact, the agonist would still be able to produce a maximal effect, if a sufficient overdose was given to displace the competitive antagonist. However, the competitive antagonist would not change the binding characteristics of the receptor for the agonist and so curve B is simply shifted to the right but remains parallel to curve A. In contrast, if a noncompetitive antagonist binds to the receptor, the agonist would no longer be able to produce a maximal effect, no matter how much of an overdose is administered (curve C). Partial agonists may produce a qualitatively different change in the receptor, whereas antagonists bind without producing a change in the receptor that results in altered cellular function.

Diagnosis of clinically unrecognized endobronchial intubation in paediatric anaesthesia: which is more sensitive kamagra polo 100 mg, pulse oximetry or capnography? Perioperative anaesthetic morbidity in children: a database of 24 100 mg kamagra polo,165 anaesthetics over a 30-month period kamagra polo 100mg. Clinical evaluation of a Raman scattering multiple gas analyzer for the operating room 100mg kamagra polo. The capnograph: applications and limitations–an analysis of 2000 incident reports . Age , minimum alveolar anesthetic concentration , and minimum alveolar anesthetic concentration-awake . Prospective randomized controlled multi-centre trial of cuffed or uncuffed endotracheal tubes in small children . Accuracy of a new low-flow sidestream capnography technology in newborns: a pilot study . The fast flush test measures the dynamic response of the entire blood pressure monitoring system. Perioperative spinal cord infarction in nonaortic surgery: report of three cases and review of the literature. Thrombotic complications of umbilical artery catheters: A clinical and radiographic study. Coarctation of the abdominal aorta and renal artery stenosis related to an umbilical artery catheter placement in a neonate. Evaluation of distal radial artery cross- sectional internal diameter in pediatric patients using ultrasound. Incidence and clinical outcome of iatrogenic femoral arteriovenous fistulas: Implications for risk stratification and treatment. Surgical intervention for complications caused by femoral artery catheterization in pediatric patients. Ultrasound-guided versus landmark-guided 1814 femoral vein access in pediatric cardiac catheterization. Complications resulting from use of arterial catheters: Retrograde flow and rapid elevation in blood pressure. Arterial fast bolus flush systems used routinely in neonates and infants cause retrograde embolization of flush solution into the central arterial and cerebral circulation. Retrograde air embolization during routine radial artery catheter flushing in adult cardiac surgical patients: An ultrasound study. Retrograde blood flow in the brachial and axillary arteries during routine radial arterial catheter flushing. Pressurized bag pump and syringe pump arterial flushing systems: An unrecognized hazard in neonates? Oscillometric blood pressure measurements by different devices are not interchangeable. Particular Requirements for the Safety, Including Essential Performance, of Automatic Cycling Non-Invasive Blood Pressure Monitoring Equipment. A comparison of two automated indirect arterial blood pressure meters: With recordings from a radial arterial catheter in 1815 anesthetized surgical patients. Comparison of two automatic methods and simultaneously measured direct intra-arterial pressure. Sampling intervals to record severe hypotensive and hypoxic episodes in anesthetised patients. Comparison of non-invasive blood pressure measurements on the arm and calf during cesarean delivery. Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures. Impact of the pulmonary artery catheter in critically ill patients: Meta-analysis of randomized clinical trials. American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Practice guidelines for pulmonary artery catheterization: an updated report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Summary of recommendations: Guidelines for the prevention of intravascular catheter-related infections. Central venous access sites for the prevention of venous thrombosis, stenosis and infection in patients requiring long-term 1816 intravenous therapy. Central venous catheters in pediatric patients—subclavian venous approach as the first choice. Minimizing complications associated with percutaneous central venous catheter placement in children: recent advances. Percutaneous femoral venous catheterizations: a prospective study of complications. Comparison of the Fick and dye injection methods of measuring the cardiac output in man. Measurement of cardiac output in anaesthetized animals by a thermodilution method. A multicenter evaluation of a new continuous cardiac output pulmonary artery catheter system. Effect of injectate volume and temperature on thermodilution cardiac output determination. Clinicians’ abilities to estimate cardiac index in ventilated children and infants. Clinical assessment of cardiac performance in infants and children following cardiac surgery. Clinical validation of cardiac output measurements using femoral artery thermodilution with direct Fick in ventilated 1817 children and infants. A comparison of pulmonary and femoral artery thermodilution cardiac indices in paediatric intensive care patients. The effectiveness of right heart catheterization in the initial care of critically ill patients. Arterial waveform analysis for the anesthesiologist: Past, present, and future concepts. Validation of the mostcare pulse contour cardiac output monitor: Beyond the bland and altman plot. Digest of the 10th International Conference on Medical and Biological Engineering; Dresden1973. Translation of Otto Frank’s paper “Die Grundform des Arteriellen Pulses” Zeitschrift fur Biologie 37: 483–526 (1899). The static elastic properties of 45 human thoracic and 20 abdominal aortas in vitro and the parameters of a new model. The impact of phenylephrine, ephedrine, and increased preload on third-generation Vigileo-FloTrac and esophageal doppler cardiac output measurements. Arterial pressure allows monitoring the changes in cardiac output induced by volume expansion but not by norepinephrine. Cardiac output measurement in patients undergoing liver transplantation: pulmonary artery catheter versus 1818 uncalibrated arterial pressure waveform analysis. Arterial pressure-based cardiac output in septic patients: Different accuracy of pulse contour and uncalibrated pressure waveform devices. Uncalibrated pulse contour- derived stroke volume variation predicts fluid responsiveness in mechanically ventilated patients undergoing liver transplantation. Uncalibrated arterial pulse contour analysis versus continuous thermodilution technique: Effects of alterations in arterial waveform. Cardiac output derived from arterial pressure waveform analysis without calibration vs. Validation study of Nexfin(R) continuous non-invasive blood pressure monitoring in critically ill adult patients. Noninvasive continuous cardiac output by the Nexfin before and after preload-modifying maneuvers: A comparison with intermittent thermodilution cardiac output. Measurement of cardiac output in children by pressure-recording analytical method. Pressure recording analytical method for measuring cardiac output in critically ill children: A validation study. Assessment of cardiac output in children: A comparison between the pressure recording analytical method and Doppler echocardiography. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Perioperative maintenance of 1819 normothermia reduces the incidence of morbid cardiac events. Inaccuracy of liquid crystal thermometry to identify core temperature trends in postoperative adults. Period analysis of the electroencephalogram on a general-purpose digital computer. Burst suppression or isoelectric encephalogram for cerebral protection: Evidence from metabolic suppression studies. Relationship between bispectral index values and volatile anesthetic concentrations during the maintenance phase of anesthesia in the B-unaware trial. Comparative effects of ketamine on Bispectral Index and spectral entropy of the electroencephalogram under sevoflurane anaesthesia. Ketamine has no effect on bispectral index during stable propofol-remifentanil anaesthesia. Effect of remifentanil on plasma propofol concentration and bispectral index during propofol anaesthesia. Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. Bispectral index monitoring in the intensive care unit provides more signal than noise. Overestimation of Bispectral Index in sedated intensive care unit patients revealed by administration of muscle relaxant. Irritant contact dermatitis after use of Bispectral Index sensor in prone position. Bispectral index monitoring to prevent awareness during anaesthesia: The B-Aware randomised controlled trial. The incidence of intraoperative awareness in children: Childhood awareness and recall evaluation. The differences in the bispectral index between infants and children during emergence from anesthesia after circumcision surgery. Quantitation of beat-to-beat changes in stroke volume from the aortic pulse contour in man. Diastolic flow reversal in the descending thoracic aorta is significant for severe aortic insufficiency. A remarkably versatile tool, real-time echocardiography provides a comprehensive evaluation of myocardial, valvular, and hemodynamic performances. These capabilities attracted the attention of anesthesiologists and surgeons challenged by the unique difficulties of perioperative cardiovascular management. Over the 30 years following the first report of intraoperative echocardiography to assess ventricular function by Barash and colleagues in 1978, echocardiography has emerged as the technique of choice for a wide variety of intraoperative case challenges. The American Society of Anesthesiologists in conjunction with the National Board of Echocardiography has established a second certification pathway in basic perioperative echocardiography, www. These efforts are unique in intraoperative monitoring and attest to the critical role that accurate and thorough echocardiographic interpretation plays in current anesthetic practice. Principles and Technology of Echocardiography Echocardiography generates dynamic images of the heart from the reflections of sound waves. The ultrasound transducer records the time delay and signal intensity for each returning reflection. Since the speed of sound in tissue is constant, the time delay allows the echo system to precisely calculate the location of cardiac structures and thereby create an image map of the heart. The resulting tissue vibrations create a longitudinal wave with alternating areas of compression and rarefaction (Fig. Vibrations of the ultrasound transducer create cycles of compression and rarefaction in the adjacent tissue. The ultrasound energy is characterized by its amplitude, wavelength, frequency, and propagation velocity. The amplitude of a sound wave represents its peak pressure and is appreciated as loudness. The intensity of the sound signal is proportional to the square of the amplitude and is an important factor regarding the potential for tissue damage with ultrasound. Since levels of sound pressure vary over a large range, it is convenient to use the logarithmic decibel (dB) scale: where A is the measured sound amplitude and A is a standard referencer sound level; I is the intensity and I is a standard reference intensity. Ther Food and Drug Administration limits the intensity output of cardiac ultrasound systems to be below 720 W/cm because of concerns of potential2 tissue injury. The propagation velocity of sound (v) is determined solely by the medium through which it passes. As the product of wavelength and frequency equals velocity: V = λ × f, it becomes apparent that the wavelength and frequency are inversely related: λ = v × 1/f and that λ = (1,540 m/s)f. High-frequency, short- wavelength ultrasound is more easily focused and directed to a specific target location. Properties of Sound Transmission in Tissue The propagation of a sound wave through the body is markedly affected by its interactions with the various tissues encountered.

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Because mostT of the perfusion is to the dependent lung 100mg kamagra polo, the V⋅/Q⋅ matching in this position is maintained similar to that in the upright position kamagra polo 100 mg. Controlled positive-pressure ventilation is the most common way to provide adequate ventilation and ensure gas exchange in an open-chest situation 100 mg kamagra polo. Frequently kamagra polo 100mg, thoracoscopy is performed using intercostal blocks with the patient breathing spontaneously to allow proper lung examination . The thoracoscope provides an adequate seal of the open chest to prevent a “free” open-chest situation . Two complications can arise from the patient breathing spontaneously with an open chest . The negative pressure in the intact hemithorax , compared with the less negative pressure of the open hemithorax , can cause the mediastinum to move vertically downward and push into the dependent hemithorax . The mediastinal shift can create circulatory and reflex changes that may result in a clinical picture similar to that of shock and respiratory distress. Sometimes, depending on the severity of the distress, the patient needs to be tracheally intubated immediately, with initiation of positive-pressure ventilation, and the anesthesiologist must be prepared to intubate in this position without disturbing the surgical field. Figure 38-5 Schematic representation of the effects of gravity on the distribution of pulmonary blood flow in the lateral decubitus position. Vertical gradients in the lateral decubitus position are similar to those in the upright position and cause the creation of West zones 1, 2, and 3. Consequently, pulmonary blood flow increases with lung dependency, and is largest in the dependent lung and least in the nondependent lung. P , pulmonary artery pressure; P , alveolar pressure; P , pulmonary venous pressure. During inspiration, the relatively negative pressure in the intact hemithorax compared with atmospheric pressure in the open hemithorax can cause movement of air from the nondependent lung into the dependent lung. This gas movement reversal from one lung 2575 to the other represents wasted ventilation and can compromise the adequacy of gas exchange. Paradoxical breathing is increased by a large thoracotomy or by an increase in airway resistance in the dependent lung. Positive-pressure ventilation or adequate sealing of the open chest eliminates paradoxical breathing. The induction of general anesthesia does not cause significant change in the distribution of blood flow, but it has an important impact on the distribution of ventilation. Most of the V enters the nondependent lung, andT this results in a significant V⋅/Q⋅ mismatch. Any reduction in volume in the dependent lung is of a greater magnitude than that in the nondependent lung for several reasons. First, the cephalad displacement of the dependent diaphragm by the abdominal contents is more pronounced and is increased by paralysis. Second, the mediastinal structures pressing on the dependent lung or poor positioning of the dependent side on the operating table prevents the lung from expanding properly. The aforementioned factors will move lungs to a lower volume on the S-shaped volume–pressure curve (Fig. The nondependent lung moves to a steeper position on the compliance curve and receives most of the V , whereas the dependent lung is on the flat (noncompliant) part of theT curve. During inspiration, negative pressure in the intact hemithorax causes the mediastinum to move downward. During expiration, relative positive pressure in the intact hemithorax causes the mediastinum to move upward. However, the upper lung is now no longer restricted by the chest wall and is free to expand, resulting in a further increase in V⋅/Q⋅ mismatch as the nondependent lung is preferentially ventilated, owing to a now increased compliance. During paralysis and positive-pressure ventilation, diaphragmatic displacement is maximal over the nondependent lung, where there is the least amount of resistance to diaphragmatic movement caused by the abdominal contents (Fig. This further compromises the ventilation to the dependent lung and increases the V⋅/Q⋅ mismatch. During two-lung ventilation in the lateral position, the mean blood flow to the nondependent lung is assumed to be 40% of cardiac output, whereas 60% of cardiac output goes to the dependent lung (Fig. Normally, venous admixture (shunt) in the lateral position is 10% of cardiac output and is equally divided as 5% in each lung. Therefore, the average percentage of cardiac output participating in gas exchange is 35% in the nondependent lung and 55% in the dependent lung. During inspiration, movement of gas from the exposed lung into the intact lung and movement of air from the environment into the open hemithorax cause collapse of the exposed lung. The induction of anesthesia has caused a loss in lung volume in both lungs, with the nondependent (up) lung moving from a flat, noncompliant portion to a steep, compliant portion of the pressure–volume curve, and the dependent (down) lung moving from a steep, compliant part to a flat, noncompliant part of the pressure– volume curve. Thus, the anesthetized patient in the lateral decubitus position has most 2578 tidal ventilation in the nondependent lung (where there is the least perfusion) and less tidal ventilation in the dependent lung (where there is the most perfusion). Opening the chest increases nondependent lung compliance and reinforces or maintains the larger part of the tidal ventilation going to the nondependent lung. To this, 5% must be added, which is the obligatory shunt through the nondependent lung. Other considerations that impair optimal ventilation to the dependent lung include absorption atelectasis, accumulation of secretions, and the formation of a transudate in the dependent lung. One-lung Ventilation Absolute Indications for One-lung Ventilation Currently, a variety of thoracic surgical procedures such as lobectomy, pneumonectomy, esophagogastrectomy, pleural decortication, bullectomy, and bronchopulmonary lavage are commonly performed. Customarily, the indications are classified either as absolute or as relative (Table 38-1). The absolute indications include life-threatening complications, such as massive bleeding, sepsis, and pus, in which the nondiseased contralateral lung must be protected from contamination. Bronchopleural and bronchocutaneous fistulae are absolute indications because they offer a low-resistance pathway for the delivered V duringT positive-pressure ventilation. A giant unilateral bulla may rupture under positive pressure, and ventilatory exclusion is mandatory. Finally, during bronchopulmonary lavage for alveolar proteinosis or cystic fibrosis, prevention of drowning the contralateral lung is necessary. Improvements in video-endoscopic surgical equipment and a growing enthusiasm for minimally invasive surgical approaches have contributed to its use. The lung should be well collapsed to provide the surgeon with an optimal view of the surgical field, and to facilitate palpation of the lesion in the lung parenchyma. In addition, it is difficult to place the stapler on a lung that is not completely collapsed, and there is an increase in incidence of postoperative air leak in these circumstances. In some institutions, 80% to 90% of the procedures are now performed using the thoracoscopic approach. Typical values for fractional blood flow to the nondependent and dependent lungs, as well as PaO2 and Q⋅S/Q⋅t for the two conditions, are shown. The Q⋅S/Q⋅t during two-lung ventilation is assumed to be distributed equally between the two lungs (5% to each lung). The 35% of total flow perfusing the nondependent lung, which was not shunt flow, was assumed to be able to reduce its blood flow by 50% by hypoxic pulmonary vasoconstriction. Upper lobectomy, pneumonectomy, and thoracic aortic aneurysm repair are high-priority indications. These procedures are technically difficult, and optimal surgical exposure and a quiet operative field are highly desirable. Nevertheless, many surgeons are accustomed to operating with the lung collapsed for these cases. These procedures include minimally invasive cardiac surgery, lung volume reduction, thoracic aneurysm repair, thoracic spinal procedures, mediastinal mass resection, thymectomies, and mediastinal lymph node dissection. It is important to distinguish between the need for lung isolation versus lung separation. Whenever the nondiseased lung is threatened with contamination by blood or pus from the diseased lung, the lungs must be isolated to prevent potentially life-threatening complications. Other indications are bronchopleural and bronchocutaneous fistulas because they offer a low-resistance pathway for the delivered V during positive-pressureT ventilation. Finally, during bronchopulmonary lavage for alveolar proteinosis or cystic fibrosis, protection of the contralateral lung from drowning is necessary. These situations, however, are relatively uncommon and in modern anesthesia practice constitute less than 10% of all thoracic procedures. This includes all the relative indications that are primarily for surgical exposure. One lumen is long enough to reach a main stem bronchus, and the second lumen ends with an opening in the distal trachea. Lung separation is achieved by inflation of two cuffs: A proximal tracheal cuff and a distal bronchial cuff located in the main stem bronchus (see “Positioning Double-lumen Tubes”). The endobronchial cuff of a right-sided tube is slotted or otherwise designed to allow ventilation of the right upper 2582 lobe because the right main stem bronchus is too short to accommodate both the right lumen tip and a right bronchial cuff. This tube design has the advantages of having D-shaped, large-diameter lumens that allow easy passage of a suction catheter, offer low resistance to gas flow, and have a fixed curvature to facilitate proper positioning and reduce the possibility of kinking. The original red rubber Robertshaw tubes were available in three sizes: small, medium, and large. These are available in both right-sided and left-sided versions and in 35 French (Fr), 37 Fr, 39 Fr, and 41 Fr sizes. The advantages of the disposable tubes include the relative ease of insertion and proper positioning as well as easy recognition of the blue color of the endobronchial cuff when fiberoptic bronchoscopy is used. Other advantages are the confirmation of the position on a chest radiograph using the radiopaque lines in the wall of the tube and the continuous observation of tidal gas exchange and respiratory moisture through the clear plastic. The right-sided endobronchial tube is designed to minimize occlusion of the opening of the right upper lobe bronchus. The right endobronchial cuff is doughnut-shaped and allows the right upper lobe ventilation slot to ride over the opening of the right upper lobe bronchus. This tube has a D-shaped wire-reinforced lumen to maintain the tip at a 45-degree angle. The reinforced wall tends to prevent obstruction or kinking of the bronchial lumen, yet at the same time maintains flexibility. This clinical scenario can be seen in patients who have previously undergone a left upper lobectomy and the expansion of the left lower lobe displaces the left main bronchus upward. It is possible to measure the diameter of the left bronchus from the chest radiograph in almost 75% of patients. In patients in whom the left main bronchus cannot be directly measured, the left bronchial diameter can be accurately estimated by measuring tracheal width. The common practice of fiberoptic bronchoscopy has decreased the risk of undetected distal placement or migration of the bronchial tip. The tracheal cuff (high volume, low pressure) can accommodate up to 20 mL of air, and the bronchial cuff can be checked using a 3-mL syringe. The tube should be coated liberally with water-soluble lubricant and the stylet should be withdrawn, lubricated, and gently placed back into the bronchial lumen without disturbing the tube’s preformed curvature. A Macintosh laryngoscope blade is preferred for intubation of the trachea because it provides the largest area through which to pass the tube. The insertion of the tube is performed with the distal concave curvature facing anteriorly. After the tip of the tube is past the vocal cords, the stylet is removed and the tube is rotated through 90 degrees. A left-sided tube is rotated 90 degrees to the left, and a right-sided tube is rotated to the right. Advancement of the tube ceases when moderate resistance to further passage is encountered, indicating that the tube tip has been firmly seated in the main stem bronchus. It is important to remove the stylet before rotating and advancing the tube to avoid tracheal or bronchial laceration. Rotation and advancement of the tube should be performed gently and under continuous direct laryngoscopy to prevent hypopharyngeal structures from interfering with proper positioning. Once the tube is believed to be in the proper position, a sequence of steps should be performed to check its location. First the tracheal cuff should be inflated, and equal ventilation of both lungs established. If breath sounds are not equal, the tube is probably too far down, and the tracheal lumen opening is in a main stem bronchus or is lying at the carina. The second step is to clamp the right side (in the case of the left-sided tube) and remove the right cap from the connector. Then the bronchial cuff is slowly inflated to prevent an air leak from the bronchial lumen around the bronchial cuff into the tracheal lumen. This ensures that excessive pressure is not applied to the bronchus and helps avoid laceration. The third step is to remove the clamp and check that both lungs are ventilated with both cuffs inflated. This ensures that the bronchial cuff is not obstructing the contralateral hemithorax, either totally or partially. The final step is to clamp each side selectively and watch for absence of movement and breath sounds on the ipsilateral (clamped) side; the ventilated side should have clear breath sounds, chest movement that feels compliant, respiratory gas moisture with each tidal ventilation, and no gas leak. If the tracheal lumen is connected to an underwater seal system, gas will be seen to bubble up through the water. The bronchial cuff can then be gradually inflated until no gas bubbles are seen and the desired cuff seal pressure can be attained. This test is of extreme importance when absolute lung separation is needed, such as during bronchopulmonary lavage. The upper surface of the blue endobronchial cuff should be just below the tracheal carina.

The infow cannula is anatomical and hemodynamic variables with two inserted in the apex of the single right ventricle and the outfow cannula at the level of the Damus-Kaye-Stansel diferent approaches [1 kamagra polo 100 mg, 2] 100 mg kamagra polo. Te correct landmark of apical as site for infow cannulation in case of inadequate cannulation must be carefully identifed 100mg kamagra polo, as previ- drainage with the apical cannula kamagra polo 100mg. Te outfow can- ous surgical adhesions and coronary abnormalities nula placement results are likewise challenging due can distort the anatomy . Right orientation of the to the previous surgically reconstructed aorta via infow cannula to the septum and accurate resec- Norwood patch and Damus-Kaye-Stansel anasto- tion of right single ventricle inner trabeculation are mosis , so that an extension with prosthetic graf can also mandatory for an optimal drainage of the be used to obtain a better alignment and orienta- heart . Te single systemic atrium can also be used tion avoiding compression by the sternum . Complications related to excessive bleeding are likely to be encoun- tered in these patients and are due to a combination of multiple previous operations and coagulation abnormalities related to multisystem failure . A higher fow is required to cope in the apex of the single right ventricle and the outfow with the increased load of the systemic single ven- cannula at the level of the Damus-Kaye-Stansel anastomo- sis . Te fundamental require- the early stages of the palliation, the small size of ment is to create a systemic venous reservoir by the patients (most likely less than 15 kg) limits the 384 F. In the acute phase, continuous fow is pref- undergoing successful transplantation in these erable as it can also allow a better unloading of the cohorts were lucky to have received a donor organ systemic ventricle, can occur throughout the in a relatively short period of time, with none of entire cardiac cycle, and can consequently pro- the survivors mechanically assisted for longer than vide higher fow than pulsatile pumps at the same 21 days. Fontan-failing As general presumption, the identifcation of patients are commonly bigger size children, ado- predominant etiology of failure may direct the lescents, and young adults, allowing the option to 38 most suitable approach to mechanically support use adult-designed implantable devices in pediat- the circulation (. Device implantation can be performed on a beating heart or inducing ventricular fbrillation, with cardioplegic arrest established when a concomitant systemic atrio-. Right sketch shows the implantation of the arterial cannula Te implantation of ventricular assist device in the proximal stump of the extracardiac conduit, the is facilitated by the loss of tripartite confgura- capacity chamber created with an enlarging patch, and the tion of systemic right ventricle. However, there connection of the superior vena cava in the capacity chamber could be difculties related to the presence of with enlargement patch. Both cannulas are brought percutaneously trabeculae in the body of morphological right and connected to a paracorporeal ventricle ventricle. Te choice of the optimal device implantation site must be carefully evaluated, by using intraoperative transesophageal echocar- previously described. Resection of an adequate amount of coarse provided frst the construction of an adequate sys- muscle trabeculation, muscle bands, and obstruc- temic venous chamber to accommodate the Syn- tive chordae is mandatory to prevent obstruction Cardia infow sewing cuf. Multiple previ- in whom their size allows the use of intracorporeal ous operations might have produced dense devices. Tird-generation continuous-fow pumps adhesions to frst of all compel peripheral cannula- have been increasingly implanted in the last tion for cardiopulmonary bypass and to also 388 F. One can argue that a lef morphologic and return of blood in the pulmonary circulation sub-pulmonic ventricle is stronger and more using a graf sutured to pulmonary artery and tun- durable without the need of mechanical support. Measures to protect the sub-pulmonic ventricle before and afer car- diopulmonary bypass weaning were considered, including nitric oxide inhalation and continuous measurement of pulmonary artery pressure. J Thorac Cardiovasc Surg systemic atrioventricular and aortic valves and 141:588–590 6. Brancaccio G, Gandolfo F, Carotti A et al (2013) absence of intracardiac shunts are mandatory Ventricular assist device in univentricular heart physi- before HeartWare implantation. Interact Cardiovasc Thorac Surg 16(4):568–569 aortic valve following implantation of contin- 7. De Rita F, Crossland D, Griselli M et al (2015) uous-fow pumps has been a cause for concern. Semin Thorac We noticed de novo aortic regurgitation in two Cardiovasc Surg Pediatr Card Surg Annu 18(1):2–6 8. In one HeartWare ventricular assist device in a patient with failed patient aortic valve replacement was eventually Fontan circulation. Prêtre R, Häussler A, Bettex D et al (2008) Right-sided univentricular cardiac assistance in a failing Fontan cir- 1. Ann Thorac Surg 86:1018–1020 circulatory support in univentricular heart: current 11. Semin Thorac Cardiovasc Surg Pediatr case of total artifcial cardiac support in failed Fontan cir- Card Surg Annu 18(1):17–24 culation after cardiectomy: is continuous fow better than 2. J Thorac Cardiovasc Surg 145:e62–e63 cardiac support in children with congenital heart dis- 12. Semin Thorac culatory support in patients with heart failure second- Cardiovasc Surg Pediatr Card Surg Annu 17(1):62–68 ary to transposition of the great arteries. J Thorac Cardiovasc Surg 147:697–705 Clinical outcomes after ventricular assist device 5. J Heart Lung Transplant 32(6):615–620 38 391 39 Continuous-Flow Pumps in Infants, Jarvik Infant System, and Destination Therapy in Pediatrics Antonio Amodeo, Sergio Filippelli, Arianna Di Molfetta, Gianluigi Perri, and R. It is a continuous-fow pump allo- cated inside the lef ventricle close to the apex. Te need for long-term mechanical support in Te blood fows into the device and then forced the pediatric population has been recognized for by a magnetically driven axial rotor into a tubular many years. Te heart transplants are performed worldwide, but pump has only one moving component: the rotor many more could be done if donors were avail- containing a permanent magnet of a brushless able. Te number of pediat- ric patients sufering from end-stage heart fail- ure is continuously increasing, and assisting 39. Tis has substantially lim- of the adult Jarvik 2000, which had achieved ited the system’s portability which has been a patient support over 3 years at the time, with barrier to hospital discharge. If we were to 39 increase the speed to maintain the necessary pres- sure, with the same blade shapes, the matching of 39. In the smaller pumps, the fow channels tenth the size of previous positive displacement become very small, and the fuid interactions pumps. In particular, axial-fow pump technology based on surface roughness and boundary layer allows tiny pumps running at high speed to efects are more pronounced (. Some parts must have 393 39 Continuous-Flow Pumps in Infants, Jarvik Infant System, and Destination Therapy 10. Machining methods and approach to optimization of the blade shapes for quality assurance were critical to success. Major hemolysis using redesigned pump blades, we hydrodynamic parameters that determine pump abandoned the 11 mm design. Te speed and torque requirements of the motor are determined by the required impeller tip velocity and the required output power of the motor. With these values known, the motors were designed using computer modeling techniques. Te infant pump that we developed was 11 mm diameter, small enough to ft a newborn, but this proved to be too small to achieve enough fow for infants over 10 kg, unless speed was increased to 32,000 rpm (. Te agency informed us that the hemolysis that occurred was unacceptably high, and the condition of the in vivo animals was not good enough for approval. Te animals showed low might be originating from the bearings at the high hemolysis. Since these animal fabricated pumps that had no impeller blades and experiments are still under way at the time of no stator blades. Tus the only sites of high shear writing this chapter, details are unavailable, but that remained were the gaps between the rotating in general the hemolysis is low, and the ani- conical ceramic bearing shaf and the tips of the mal’s condition has been excellent except in supporting posts. To keep the speed as low as possible, we decided to increase the diameter of the pump from 11 to 15 mm, named infant Jarvik 2015 (. Increasing the diameter of the pump increa- ses the cross-sectional area of the fow path, b reduces resistance, and increases fow. Increasing the diameter also increases the tip speed at a given rotational speed, which allows the pump to operate at a lower speed for a given pressure. Lower speed permits the pump to avoid blood damage caused by high shear at the bearings. Most animals were healthy, appeared Bambino Gesù Hospital in Rome for a compas- normal, and were free of any serious pump-related sionate use in a 1-year-old male afected by an problems. Lab values were also essentially normal idiopathic dilated cardiomyopathy in 2012. Terefore, for compassionate use, shorten expectancy of life related to the primary the patient was treated implanting an infant Jarvik disease such as Duchenne’s patients and other pump (. In the mean- most challenging elements in the management of time the patient recovered from the infection, and patients afected by Duchenne muscular dystro- 7 days later it was possible to implant another phy. Te efcacy of standard ing: orthopedic, gastroenterology, radiologic, heart failure treatment for improving the clinical respiratory, psychological, anesthesiological, ethi- outcome of these patients has been proven, but cal, and cardiac assessments. Duchenne patient-centric care requires that the patient and syndrome has generally been considered a con- the family are sufciently educated about the traindication for cardiac transplantation due to alternatives available so that their expectations the associated progressive skeletal myopathy can be met as fully as possible. Tis is routinely performed to assess the area of the concern has resulted in a reluctance to ofer car- skull where the pedestal should be inserted (bone diac transplantation to these patients in an era of thickness should be at least 5 mm). Te recent advances in lef ven- that the use of pedestal in patient on wheelchair is tricular assist devices, used as destination ther- preferable and more comfortable, thus reducing apy, have made feasible the use of such devices the cable infection [13]. Baseline assessments of the performed on beating heart cardiopulmonary cardiac involvement should be performed frst at bypass except in one case carried out by minimally the age of 6 years and once every 2 years until the invasive approach through lef mini-thoracotomy age of 10. Amodeo A, Adorisio R (2012) Left ventricular assist device care is very high even when discharged home in Duchenne cardiomyopathy: can we change the natu- because of all comorbidities (non-deambulating ral history of cardiac disease? Competing clinical experience with the Jarvik 2000 implantable risks for death and cardiac transplantation in chil- axial-fow left ventricular assist system. Circulation dren with dilated Cardiomyopathy: results from the 105(24):2855–2856 pediatric cardiomyopathy registry. Circulation therapy in cardiac end stage dystrophinopathies: mid- 127(16):1702–1711 term results. Brancaccio G, Filippelli S, Michielon G, Iacobelli R, learned from the frst applications. Seguchi O, Kuroda K, Fujita T, Fukushima N, Nakatani T G, Parisi F, Carotti A, Amodeo A (2012) Ventricular (2016) Advanced heart failure secondary to muscular assist devices as a bridge to heart transplantation or dystrophy: Clinical outcomes after left ventricular assist as destination therapy in pediatric patients. Christensen, Christina VanderPluym, Jennifer Conway, Angela Lorts, Holger Buchholz, Tomas Schlöglhofer, Juliane Viericke, Alexander Stepanenko, Friedrich Kaufman, and Gro Sorenson Chapter 45 Psychosocial Considerations of Mechanical Circulatory Support: Decision Making, Behavioral Evaluation, Quality of Life, Caregivers, and End of Life – 467 Kathleen L. Although this practice is widely dynamic training, resistive training, and work on experienced in end­stage heart failure popula­ the respiratory muscles [18, 19]. First Ten Days) Postoperative complications of physiotherapic interest are mainly represented by infections, Physiotherapeutic intervention takes place at bleeding, thromboembolic events, device mal­ every phase during the postoperative recovery, function, and depression [17]. Physiotherapists are substantially difer from common cardiac surgery actively involved in the pathway of care, and they 40 patients, as the main goals are related to the treat­ are recognized as a key fgure within the multidis­ ment/prevention of postoperative pulmonary ciplinary team in order to achieve patient recov­ complications, in the early phase. To this care, considering the patient mental status, the end, in the frst 24/48 h or afer extubation, and/or patient’s cooperation, and stability of the vital when sedation is reduced and then stopped, an signs. It should not be forgotten that physiother­ early physiotherapeutic evaluation process should apeutic duties can be diferent around the world: start. Te bedside evaluation will consist in in example, respiratory treatment is usually observing the respiratory pattern: Is chest dyna­ carried out by respiratory therapist, and physi­ mic altered? Is the patient breathing spontane­ cal rehabilitation is instead provided by physi­ ously? Is pain countries, physiotherapists are normally entitled preventing appropriate breathing? Are pulmonary to provide both respiratory and physical rehabili­ secretions present, and, if yes, is patient able to tation. Efective coughing can also stable, patient is assisted out of the bed to a chair play an important role in the secretions clearance: [22]. A pillow evaluate if any defcit is present and to stimulate embraced with the arms while coughing is usually further active movements. Indeed, enhancing well accepted in order to reduce chest pain during patient in­bed positioning can play an important cough. On the other hand, pleural efusion and postural passages and improving autonomy of dysventilation phenomena, requiring physiothera­ daily activities. Monitoring of the pulmonary peutic intervention, are common afer cardiac sur­ function still remains an important aspect. To this end, respiratory this end, continuing evaluation of the chest imag­ therapy should be proposed including deep breath­ ing, together with the clinical observation, should ing exercises and secretions clearance techniques. Te major objective to be pursued by lung dysventilation must be also prevented/ means of respiratory exercises is to encourage treated by means of a respiratory program patients to perform deep breathings in order to focused on respiratory exercises (. To this end, in uncomplicated patients, treatment, respiratory therapy can be continued the blow­bottle device can be used as soon as the by means of incentive spirometry exercises, in subject is awake and sedation stopped. Blow bottle order to encourage deep breathings and enhance is a respiratory device used to allow lung expansion diaphragmatic excursion and chest wall expan­ in postsurgical setting. Tis practice, during the initial postopera­ be built up using material commonly available in tive timeframe, also contributes to obtain the hospital wards, such as a saline bottle and a chest active patient involvement. Respiratory exercises 40 drain tubing (length 20–30 cm, >30 cm) [25, 26] can be scheduled during the day in more than (. Te patient is asked to make an inspi­ one session; once the patient is trained on the use ration and then blow into the tube: during the expi­ of the incentive spirometry device, the exercise ration, the water contained in the bottle provides an can be performed autonomously. Te blow­bottle respiratory since the degree of patient’s mobility normally exercises, a simple and feasible technique, can be increases during this phase, there is also the need used in the frst postoperative days, when needed. A saline bottle (500 ml) is be closed preventing exit of water even while patient opened and drained to the desired level of water b, and is resting. The set should be replaced frequently in then the bottle is closed and a tube is inserted into the order to guarantee adequate sanitation water through a slot b, c formed on the container. Exercise is stopped in case of subjective intoler­ ance or drop in systolic pressure. Physiotherapist must be trained in emergency procedures in case of device malfunctioning and must be also aware of patient hemodynamic instability and device dislodgement during mobilization [22]. When postural passages, who have not yet started, should be encouraged upright position, and in­bed movements are car­ beginning with the maintenance of a sitting posi­ ried out autonomously, patient is ready to walk tion at the edge of the bed, progressing toward with or without a walking frame. Ten, the patient on toes, bending knees, cycling, climbing stairs, can start a more intensive muscular program ori­ and other exercises should be supervised ented to develop the ability to gain autonomously (. Patients who were already confdent events and no deterioration of the ventricular with the exercise may be facilitated; hemody­ function. Based on the physiological namic stability is needed in order to proceed understanding of the Fick equation, O2 with the exercise’s intensity [28].

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