Douglas T. Cromack, MD

Device generator pocket infection with microorganism tracking along the transvenous leads to involve intra-cardiac portion of the electrode muscle relaxant pregnancy category generic 50 mg azathioprine free shipping. Hematogenous seeding of the transvenous leads or device generator pocket from bloodstream infection from a remote focus spasms jerking limbs azathioprine 50 mg order overnight delivery. Infection of the generator pocket could occur at the time of device implantation or during device manipulation (generator exchange/upgrade or lead revision/manipulation) muscle relaxant drugs z buy azathioprine from india. Device pocket can also get contaminated and infected if the generator or leads erode through the skin spasms neck azathioprine 50 mg with mastercard. Occasionally it may not be possible to distinguish whether indolent device infection is the cause of skin erosion or the result of generator or lead erosion spasms with fever discount 50 mg azathioprine with mastercard. Possibility of bacterial contamination of the device generator at the time of implantation was studied in an investigation by Da Costa et al. In 2 of the cases Staphylococcus schleiferi was isolated, which was molecularly identical to the strain initially found in the pacemaker pocket, suggesting that pocket contamination occurred at the time of implantation [20]. Unlike staphylococci, gram-negative bloodstream infections typically do not result in hematogenous seeding of the device leads. Both the confirmed cases had a generator site infection, suggesting that device was the source of bloodstream infection. There were no cases of hematogenous seeding of leads by gram-negative bacteremia from a distant focus. Various bacteria have different virulence factors that enable them to attach to a foreign device. Once bound to prosthesis surfaces, staphylococci establish a biofilm (slime layer) which is a surface-associated community of one or more microbial species that are firmly attached to each other and the solid surface. They are encased in an extracellular polymeric matrix that holds the biofilm together [25]. Organisms in a biofilm are more resistant to antimicrobial therapy possibly due to the physical protection from the layer of matrix which encases them [27]. Moreover, low metabolic activity and slower rate of replication of bacteria encased in the biofilm makes them more resistant to killing by cell-wall active agents (beta-lactams and glyclopeptides) that primarily target rapidly replicating bacteria. Device Related Factors Physical and biochemical properties of the polymer used to make the device generator shell, lead insulation material and electrode tips can play a vital role in allowing or inhibiting bacterial adhesion. One of the main parameters that predict bacterial adhesion is the degree of hydrophobicity of the device surface. The higher the hydrophobicity of surface material, the greater the bacterial adhesion [25, 28]. The impact of choice of device materials on the risk of infection is not well characterized and should be explored. Up to 7 % of the cultures were negative, primarily due to prior exposure to antibiotics. In the first few weeks after implantation, device infections are predominantly due to S. The prevalence of methicillin resistance among the staphylococci species causing device infections varies based on the geographical location and various studies have shown different rates [30, 33]. Patients with pocket site infections typically present with pain, erythema, drainage, swelling, tenderness or dehiscence at the site of the generator. As device leads are in close proximity to tricuspid valve, right-sided endocarditis can develop with septic emboli to lungs. Majority (81 %) of the patients presented with fever and 149 (84 %) had positive blood cultures. The tricuspid valve was most frequently involved (43 cases) and the pulmonic valve being the least affected (one case only). A positive culture (either blood or lead culture) was obtained in 53 out of 60 cases (88 %). In a retrospective study from Sweden that included 44 episodes of pacemaker endocarditis, 38 patients presented with fever without any other focal signs of device infection. Fourteen percent of the cases had systemic embolic phenomenon, with lungs being the most common site [22]. All the patients undergoing routine hemodialysis presented with bloodstream infections in this series and 77 % of the patients had fever and leukocytosis on presentation. Differentiating a lead thrombus from "true" vegetation on the basis of echocardiography can be very difficult. The scan also helped in outlining the extent of infection by showing if the infected area involved only the generator pocket or affected the leads as well. It was found to have a sensitivity of 94 % and a negative predictive value of 94 % [43]. No activity was seen in patients in Group C and minimum activity was seen in Group B patients. Six patients were found to have superficial infection and were treated with antibiotics only. Only one false positive was seen, in a patient who had a Dacron pouch in place around the generator [47]. Hence the reliability of this approach in patients with an antibiotic mesh or envelope is not known. It is also unclear how prolonged use of antibiotics would affect the results of this particular imaging modality. Identification of the causative microorganisms is critical for choosing optimal antimicrobial therapy. Therefore, once the decision has been made to remove the device, cultures of the pocket tissue, deep pocket swab, and device surface swab should be obtained at the time of extraction. In the case of pocket site infections, culture of tissue from the pocket has a higher yield than swabs from the pocket site [48]. Also, lead tip cultures are not always reliable in the presence of a pocket infection as lead tips can potentially get contaminated during extraction through an infected pocket environment [49]. Sonication of the extracted device to disrupt biofilm on the device surfaces can improve the microbiological diagnosis of infection. In the infected group, significant bacterial growth was observed in 54 % of sonicate fluids, significantly greater than the sensitivities of pocket swab (20 %), device swab (9 %), or tissue (9 %) culture. Of note, majority of patients had received antibiotics prior to device removal in this study. Therefore, sonication may be the only way to confirm lead infection in patients who have positive blood cultures but no signs of pocket infection and no lead vegetations noted on echocardiography. Management No randomized clinical trials have been conducted to compare medical management only versus device removal along with antimicrobial therapy. Overall treatment failure (death, infection recurrence) was more common in cases with device retention (52 %) versus complete device removal (25 %). Infected device removal should be done if the patient is hemodynamically stable to tolerate lead extraction procedure. However, a plan on how the patient will be "bridged" prior to re-implantation should be in place. Empiric gram-negative coverage with an anti-pseudomonas agent may also be considered in patients who present with severe sepsis or shock. A antimicrobial therapy can then be modified on the basis of culture and in-vitro susceptibility data as they become available. If the cultured organism is oxacillin susceptible and the patient does not have a beta lactam allergy, then vancomycin can be discontinued and cefazolin or nafcillin inititated. For gram negative and other organisms the therapy needs to be modified accordingly. In patients with prosthetic valve involvement, gentamicin for first 2 weeks of therapy and rifampin for the entire duration of therapy should be added to the regimen if infection is caused by staphylococci. There are limited data looking at the optimal duration of antibiotic therapy in this patient population. It is generally recommended that the patient should be treated for at least 2 weeks after removal of the infected cardiac device. The antimicrobial therapy should also be prolonged if the patient has evidence of valvular endocarditis, osteomyelitis or septic emboli. Lead Extraction Extraction of infected leads is a procedure that electrophysiologists and cardiac surgeons are encountering with a higher frequency in their practice today. However, leads that have been in place for longer periods of time tend to develop a fibrotic encasement and their removal is more complex. Attempts to remove these leads using stylus and manual traction alone can result in lead breakage, leftover lead fragments and potential damage to the heart. These older leads are now removed using extraction dilators and power sheaths [30]. These power sheaths employ a radio-frequency probe or laser, attached to the tip of the sheath that is threaded transvenously over the lead. This helps in breaking scar tissue and enables subsequent removal of the lead [59, 60]. Regardless of equipment used, lead extraction is an intricate procedure that can be associated with serious complications such as bleeding, stroke, pulmonary embolism and even death [59, 60]. Complicated device removal is associated with an increase in 30-day patient mortality [52, 56]. However, the benefit of device removal outweighs the risks associated with retention of device in most circumstances. As power sheaths are advanced over the leads, vegetations attached to lead break off and embolize to the pulmonary vasculature. In our experience, most infected leads can be safely removed percutaneously even if the vegetation size is up to 2 cm [12]. Few patients may experience transient hypotension during the procedure or post-operatively but clinically significant pulmonary embolism is rare. However, for lead vegetation size >2 cm, cardiac surgery consultation should be sought when planning lead extraction. Otherwise open-heart surgery is reserved for cases where percutaneous lead extraction is unsuccessful or not an option due to presence of very large vegetations (>2 cm) [30, 33, 53] due to concern for potential pulmonary embolism [33]. The choice of suppressive antimicrobial therapy should be guided by susceptibility testing. In cases of multi-drug resistant organisms, options for long-term oral antimicrobials can be limited and infectious diseases physician should be consulted to guide therapy. There is a paucity of data regarding the optimal duration or dosage of therapy in this population. Additionally placing patients on long-term suppressive therapy raises the risk of selection of more resistant organisms and C. Data regarding relapse of infection in these patients while on long term antibiotic therapy are also not available. Published data suggest that up to 30 % of the patients no longer need a new cardiac device after removal of an infected device [53]. Occasionally, it may be due to lack of an appropriate indication at the time of initial device placement. It is typically recommended that the patients should not undergo the replacement procedure until their blood cultures (drawn after removal of the device), have been negative for a minimum of 72 h [33, 53]. However, for a patient who has evidence of valvular endocarditis on echocardiography, it is recommended that a new device should not be implanted for at least 2 weeks [33, 53]. If the new device has to be implanted on the same side as the current infection, then a tunneled lead should be placed in the abdomen subcutaneously. Device infection resulted in two-fold higher in-hospital mortality in one investigation [4]. In a cohort of Medicare beneficiaries, the increased risk for mortality in patients with 200 S. Predictors of long-term mortality (>30 days) included renal dysfunction, system revision, malignancy, older age, and all factors affecting short-term mortality. Every 10-year increase in age was also associated with a 20 % increase in risk of death [63]. Moreover, these infections are associated with significant financial burden for patients and payers. In one study, the standardized adjusted incremental and total admission costs for infection were $14 14 Cardiac Device Related Endocarditis 201 360­$16 498 and $28 676­$53 349 for pacemakers and implantable cardioverterdefibrillators respectively [66]. There is no evidence to suggest that use of postoperative antibiotics has any utility in prevention of infection. The use of prophylactic antibiotics to prevent secondary seeding of cardiac devices from invasive dental, gastrointestinal or genitourinary procedures is also not recommended [25]. Use of an antimicrobial pouch or envelope, impregnated with minocycline and rifampin, that elutes antibiotics locally at the generator site was associated with reduced risk of pocket infections in a retrospective study where the infection rate within the first 6 months was significantly lower in patients who received the envelope (1. The world survey of cardiac pacing and cardioverter defibrillators: calendar year 2001. Cardiac device implantation in the United States from 1997 through 2004: a population-based analysis. Increasing rates of cardiac device infections among medicare beneficiaries: 1990­1999. Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study. Permanent pacemaker and implantable cardioverter defibrillator infection: a population-based study. Infections after cardioverter-defibrillator implantation: observations in 335 patients over 10 years. Infection after pacemaker implantation: infection rates and risk factors associated with infection in a population-based cohort study of 46299 consecutive patients. Renal insufficiency and the risk of infection from pacemaker or defibrillator surgery.

These dedicated noninvasive ventilators generate high gas flow muscle relaxer kidney azathioprine 50 mg buy without a prescription, can cycle between a high inspiratory pressure and a lower expiratory pressure spasms during bowel movement azathioprine 50 mg mastercard, and can sense and respond to patient inspiratory effort muscle relaxant pictures purchase azathioprine paypal. In reality quetiapine spasms order azathioprine with a visa, separation from mechanical ventilation is more a function of the resolution of the cause of respiratory failure muscle relaxant not working azathioprine 50 mg order online, rather than the technique used to withdraw ventilatory support. Thus, the process of separation from mechanical ventilation is expedited when respiratory therapy­driven protocols are used that focus on daily assessment of the ability to breath without assistance, assuming improvement of the inciting process, adequate oxygenation, and hemodynamic stability. These mechanics and gas exchange abnormalities create a challenge in terms of optimizing mechanical ventilation, because maintenance of adequate oxygenation and carbon dioxide elimination are both problematic. In addition, although the ratio of PaO2 to FiO2 (P/F ratio) does not appear to predict mortality, high dead space fraction does, and may reflect the extent of pulmonary vascular injury. Areas of dense opacification are frequently confined to the posterior, dependent portion of the lung, leaving a small, relatively normal, recruitable volume available for ventilation. In regards to the latter, it is critical that tidal volumes and static ventilatory pressures are minimized in order to avoid further injury to the remaining relatively uninjured lung. A large, randomized, prospective trial found that a small tidal volume (6 mL/kg or less) and low static (plateau) airway pressure (30 cm H2O) resulted in a relative mortality reduction of 22% when compared to a control group ventilated with tidal volumes of 12 mL/kg. Of these techniques, prone positioning alone is associated with improved survival. However, this intervention is not associated with improved outcomes, as confirmed in a recent meta-analysis. Inhaled vasodilators may be useful as "rescue" therapy in selected patients with severe, refractory hypoxemia, although outcome benefits have not been established. Furthermore, the group receiving methylprednisolone had more ventilator-free days and shock-free days at day 28, in addition to improved oxygenation and respiratory system compliance. The reasons for the lack of improvement in outcome are unclear, but likely include insensitive means for identifying patients with incipient renal failure and lack of effective preventive and therapeutic measures. If contrast must be used, low- or iso-osmolar contrast agents, pre- and postcontrast exposure intravascular volume expansion with saline or sodium bicarbonate solutions, and possibly the use of oral (but not intravenous) N-acetyl cysteine may be useful. Endocrine Aspects of Critical Care Medicine Glucose Management in Critical Illness Hyperglycemia is commonly encountered in critically ill patients and occurs in both diabetics and nondiabetics. Hyperglycemia results primarily because of increased glucose production and insulin resistance caused by inflammatory and hormonal mediators that are released in response to injury. Hyperglycemia may also be aggravated by various therapeutic and supportive interventions, including the use of corticosteroids and total parenteral nutrition. Although the risks of hyperglycemia for patients with diabetes who are ketosis-prone have long been appreciated, hyperglycemia is also detrimental to critically ill patients in a broader sense. Unfortunately, the benefits of the initial trial were not reproduced in multiple subsequent trials, and in fact an increased risk of hypoglycemia and associated harm have been observed. Adrenal Function in Critical Illness the stress response to injury includes an increase in serum cortisol levels in most critically ill patients. The diagnosis of adrenal insufficiency in critical illness is complicated by limitations of commonly used tests of adrenal function. Cortisol is highly protein bound, and serum proteins, including albumin, are commonly depressed in critically ill patients. Although total serum cortisol levels are low in critically ill patients with hypoproteinemia, free cortisol levels are elevated. However, until free cortisol assays are more widely available, the diagnosis of adrenal insufficiency in critical illness must be based on clinical suspicion and total cortisol levels. Evidence for a mortality benefit is unclear, with some trials showing improved mortality and others showing lack of efficacy. A 2015 meta-analysis suggests that there is currently low quality evidence supporting a small mortality benefit with the use of low-dose hydrocortisone (200 to 300 mg/day or equivalent) in sepsis, but that the incidence of metabolic derangements is also increased. Depression of T3 occurs within hours of injury or illness and can persist for weeks. Low hormone levels may occur for a variety of reasons, including altered binding and metabolism early in the course of illness, and depressed neuroendocrine function with more prolonged courses. Furthermore, it is not clear whether replacement of thyroid hormones is indicated or beneficial in critical illness. T3 administration to brain-dead organ donors appears to improve hemodynamic stability, although randomized trials have found minimal or no benefit to T3 or T4 administration in patients undergoing cardiopulmonary bypass and cardiac surgery. Larger, randomized prospective trials are necessary to define the role of routine thyroid hormone supplementation in nonthyroidal illness. Importantly, true hypothyroidism may be present in the critically ill, particularly in the geriatric population, and should be considered in the face of refractory shock, adrenal insufficiency, unexplained coma, and prolonged, unexplained respiratory failure. Anemia and Transfusion Therapy in Critical Illness Anemia is a frequent if not obligate accompaniment of critical illness. The cause of anemia in critical illness is multifactorial, and related to blood loss from the primary injury or illness, iatrogenic blood loss due to daily blood sampling, nutritional deficiencies, and marrow suppression. In unstressed subjects, severe anemia (Hb of 5 g/dL or less) is amazingly well tolerated due to physiologic compensations that maintain oxygen delivery and extraction. However, it has long been assumed that critically ill patients have less efficient compensatory mechanisms and reduced physiologic reserve, and thereby require a higher Hb concentration than unstressed individuals. A similar trial in pediatric patients found no mortality difference between restrictive and liberal transfusion strategies, suggesting that a restrictive strategy is safe in critically ill children. Prevention of anemia in critical illness is an appealing alternative to transfusion. As noted earlier, iatrogenic blood loss is a major factor in the development of anemia of critical illness. Another potential approach is the administration of recombinant erythropoietin and iron. Poor nutritional status is associated with increased mortality and morbidity among critically ill patients. Therefore, appropriate nutrition is an important aspect of critical care and adequate nutritional support should be considered a standard of care. Feeding intolerance due to high gastric residual volume can be improved by the administration of gastric prokinetic agents and positioning an enteric tube postpyloric. This effect appears more likely in surgical patients, such as those with burns and those who are in trauma. Specific enteral formulations, particularly those with high concentrations of glutamine, have the strongest data to support their use. Although individual medications frequently provide multiple pharmacodynamic effects, including sedation, analgesia, and anxiolysis, it is helpful to think about these effects separately when selecting medications for an individual patient. For instance, painful procedures such as the insertion of indwelling catheters, endotracheal tubes, and thoracostomy tubes require analgesia, but often do not require anxiolysis or sedation. Conversely, agitated delirium or acute alcohol withdrawal do not require analgesia and are more appropriately treated with sedatives. The patient with an ideal level of sedation and analgesia is at reduced risk for dislodging catheters, removing monitoring devices, or falling out of bed. They are more likely to be synchronous with the mechanical ventilator, which improves oxygenation and reduces the risk of lung injury. They are also better able to participate with care, early mobilization, and physical and occupational therapy. Therefore, it is important to titrate medications according to established therapeutic goals and reevaluate sedation requirements frequently. Features common to all of these scales are the ability to grade sedation over different depths and allow for indicators of agitation. The important point regarding assessment scales for pain, sedation, and delirium is that an assessment utilizing a validated scoring system should be made before and after every intervention to assess progress in achieving treatment goals. However, propofol, midazolam, and dexmedetomidine are the most commonly used hypnotic-anxiolytics. Each of these drugs has its own particular advantages and disadvantages, and detailed discussions of their properties can be found in Chapters 19 and 20. Dexmedetomidine is unique in that its mechanism of action is profoundly different from that of propofol and benzodiazepines. It provides sedation without inducing unresponsiveness or coma, may have some analgesic effects,200,201 and has little affect on respiratory drive. Generally speaking, however, dexmedetomidine is effective for patients who do not require deep sedation. Because it does not reliably produce amnesia, it is not appropriate as a solo hypnotic-anxiolytic in patients requiring paralysis. Propofol is generally more effective in these settings, but can cause hypertriglyceridemia and lead to the potentially lethal "propofol infusion syndrome. Neither randomized nor retrospective data 4127 support dexmedetomidine use in patients with alcohol withdrawal, in terms of meaningful clinical outcome. Although the aforementioned physiologic rationale for the choice of a certain regimen exists, certain regimens may be superior in terms of patient outcomes of untoward neurocognitive effects, time on the ventilator, and length of stay. A large, well-conducted study204 (two separate arms, no institutional cross-over) comparing dexmedetomidine with either propofol or midazolam demonstrated noninferiority for dexmedetomidine, although patients receiving propofol required less rescue sedation than those receiving dexmedetomidine. When compared to midazolam, dexmedetomidine may also be associated with a small reduction in the duration of mechanical ventilation, and it appears to provide significantly better patient responsiveness and cooperation compared to both drugs. Conversely, patients receiving dexmedetomidine were twice as likely as patients receiving propofol to have had cardiovascular instability. A trend toward higher mortality was observed in the dexmedetomidine group, but disappeared when all dexmedetomidine patients were compared to all propofol and midazolam patients. Interestingly, there was no difference between dexmedetomidine and midazolam on measures of agitation and delirium, whereas the difference between dexmedetomidine and propofol was statistically significant. A meta-analysis including 27 randomized trials comparing propofol versus midazolam suggested that tracheal extubation occurred earlier with the use of propofol for patients who were ventilated for a duration shorter than 36 hours. Greater levels of hypotension and elevated triglyceride levels were observed with the use of propofol. Like dexmedetomidine, opiates do not reliably produce amnesia, and are not appropriate as single agents in patients who require paralysis. Morphine should be avoided in patients with renal failure due to active metabolites that accumulate in the presence of impaired 4128 renal function. A single trial has demonstrated a benefit in mortality and ventilator-free days, but routine use is discouraged until these results are validated. Delirium and Neurocognitive Complications Neurocognitive complications including delirium and prolonged cognitive dysfunction are associated with a number of sedative medications, and may be more common in patients treated with deeper levels of sedation. The distinguishing characteristics of delirium include an acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. Although some literature supports the notion that benzodiazepine use may be associated with an increased frequency of delirium, two well-conducted trials failed to show a reduction in delirium in patients randomized to dexmedetomidine compared to benzodiazepine. The 4129 only randomized, controlled trial of such use did show a reduction in periods of delirium with regular quetiapine administration, but the study was small. A systematic review of a number of pharmacologic prevention or treatment strategies. Approximately one-third will have signs and symptoms of cognitive dysfunction 12 months after discharge. Further, long-term follow-up of patients enrolled in sedation trials has not found sedation regimens promoting light sedation or daily awakening to be associated with increased long-term cognitive, psychological, or functional problems. At some level, nosocomial infections are unavoidable and occur because of the nature of intensive care-patients are critically ill with altered host defenses, they require invasive devices (endotracheal tubes, intravascular catheters, etc. On the other hand, many nosocomial infections are preventable with relatively simple interventions. Sinusitis Radiographic sinusitis is common in critically ill patients with indwelling oral and nasal tubes. Nasotracheal intubation confers a greater risk than does orotracheal intubation of radiographic sinusitis, occurring in approximately 95% and 25% of patients with nasal and oral tubes after 1 week of intubation, respectively. Prevention of sinusitis should focus on efforts to improve sinus drainage, including semirecumbent positioning and avoidance of nasal tubes. If radiographic sinusitis is documented, any nasal tubes should be removed, and nasal irrigation and short-term administration of nasal decongestants should be considered. If the patient is severely ill, broad-spectrum antibiotic coverage should be considered. If these maneuvers do not result in resolution of signs and symptoms of sinusitis in 2 to 3 days, otolaryngologic consultation and consideration of sinus drainage procedures may be undertaken. In general, early-onset organisms are associated with zero or low attributable mortality, whereas late-onset organisms, particularly Pseudomonas and Acinetobacter species, are associated with higher mortality. The simplest and least expensive interventions are strict handwashing between patients, and semirecumbent 4132 positioning of the patient (head-of-bed angle at 30 degrees or greater from horizontal). The use of acid suppression therapy to prevent gastrointestinal bleeding is more controversial. Thus, gastrointestinal acid suppression therapy may be reserved for high-risk patients, and sucralfate may be considered as an alternative agent to acid-suppressive regimens despite its potentially reduced effectiveness. Invasive strategies typically involve collection of either tracheal aspirate specimens or bronchial­alveolar specimens using lavage or protected brushes, and then quantitating bacterial growth in the laboratory. Antibiotics can then be narrowed in spectrum or discontinued altogether depending on the results from quantitative cultures after 48 to 72 hours (Table 57-6). This approach is known as "de-escalating therapy" and is designed to ensure adequate antibiotic treatment up front, but avoid overuse of antibiotics in the long term. It is unclear whether intermediate courses of therapy would have avoided infection recurrence. However, the incidence of bacteremia is affected by several factors, including the conditions and technique of insertion, type and location of catheter, and the duration of catheterization, and can vary widely from study to study. This includes pre-insertion handwashing, full gown and gloves, and the use of a large barrier drape. However, routine catheter replacement at 3 or 7 days does not reduce the incidence of infection, and results in increased mechanical complications. Catheters coated with either antiseptics (chlorhexidine and silver sulfadiazine) or antibiotics (rifampin and minocycline) reduce bacterial colonization of catheters as well as bacteremia. Routine flushing of catheter ports with heparin reduces both the incidence of thrombosis and infection.

For patients presenting with acute leukaemias muscle relaxant drugs medication buy azathioprine now, leukapheresis may be used as an interim measure until the chemotherapy exerts its full effect muscle relaxants yellow azathioprine 50 mg purchase with visa. For patients with hyperviscosity due to elevated immunoglobulins (often IgM or IgA) back spasms yoga discount azathioprine 50 mg without a prescription, plasmapheresis is effective in reducing the paraprotein concentration spasms while eating purchase azathioprine from india. This may be necessary at disease presentation muscle relaxant yellow pill with m on it 50 mg azathioprine purchase mastercard, but can also be performed at regular intervals in symptomatic patients with chemotherapy refractory disease. For patients with polycythaemia, isovolaemic venesection will reduce the blood viscosity. Recurrent episodes of acute, severe pain due to vaso-occlusive sickle cell crises are the hallmark of these diseases (Table 14. Crises can also result from marrow aplasia, splenic or hepatic sequestration and episodes of haemolysis. The chest syndrome and the girdle syndrome are more severe forms of crisis associated with higher morbidity and mortality. Dehydration, infection, stress or skin cooling may precipitate vasoocclusive crises. Sickling of the red cells occurs in the small vessels resulting in decreased tissue blood flow and hypoxia and acidosis, which in turn precipitate further sickling. Management, therefore, includes the maintenance of a high fluid intake (60 mL/kg/24 h) to prevent dehydration and oxygen therapy if hypoxia is confirmed on pulse oximetry. Imperative to the management of patients with sickle cell crises is adequate pain relief. This often requires opiates, given as continuous intravenous or subcutaneous infusions. Sickle cell patients are functionally asplenic, and broad spectrum antibiotics should be started in any patient in whom infection is suspected. Top-up blood transfusions are often unnecessary and should be reserved for patients with signs or symptoms attributable to anaemia, typically when the Hb has fallen more than 2 g/dL and is < 5 g/dL. Transfused red cell products should be matched for Rh (C, D and E) and Kell antigens. Exchange transfusions aim to reduce the level of Hb S to < 30% and are indicated in patients with severe chest syndrome, suspected cerebrovascular events, priapism or multiorgan failure. Any patient requiring an exchange transfusion should be discussed with a haematologist. Sickle cell crisis the sickling disorders result from the inheritance of structural haemoglobin (Hb) variants. The neurological signs accompanying cord compression vary according to both the rapidity of the development of compression and the area of the cord affected (Box 14. Acute lesions often result in hypotonia and weakness, whereas chronic lesions are more often associated with the classic upper motor neurone signs of hypertonia and hyper-reflexia. The site of the lesion defines the associated sensory loss, and hyperaesthesia may be seen in the dermatome at the level of the lesion. More lateral lesions may result in dissociated sensory loss, that is, ipsilateral loss of joint position sense, and proprioception with contralateral loss of pain and temperature. Bladder and bowel disturbances often occur late, with the exception of the cauda equina compression syndrome, in which they are an early feature. If cord compression is suspected, the definitive investigation is an urgent magnetic resonance scan. Plain spinal X-rays are useful if myeloma is suspected to demonstrate lytic lesions. In the acute presentation, high-dose dexamethasone, for example, 4 mg four times daily, is given. In a patient presenting de novo phoma or plasmacytoma, or a consequence of spinal instability from lytic bone disease in multiple myeloma. Most patients with cord compression complain of pain, which is constant and can be easily confused with degenerative disease. Commonly, signs consistent with root compression, with pain in the affected dermatome, precede the overt signs of cord compression. Interim supportive measures include intravenous hydration, oxygen therapy and correction of the coagulopathy. Platelet transfusions are generally indicated when the count is < 50 × 109/L, fresh frozen plasma to replace clotting factors when the international normalized ratio or activated partial thrombin ratio is > 1. Further management will then depend on the underlying cause, and will often involve a combination of chemotherapy and radiotherapy. These coagulant proteins overcome the normal physiological anticoagulant mechanisms. The overall result, irrespective of the cause, is widespread tissue ischaemia (due to clot formation, thrombi) and bleeding (due to consumption of clotting factors, platelets, and the production of breakdown products that further inhibit the coagulation pathway). The syndrome is characterized by the formation of platelet microvascular thrombi, which primarily affect the renal and cerebral circulations. Before commencing plasma exchange, a vascular catheter will need to be inserted, but platelet transfusions should be avoided, even in cases with a severe thrombocytopenia, because these patients rarely bleed, and the addition of allogeneic platelets can lead to further platelet aggregation and worsen the underlying condition. Plasma exchange should be continued daily until at least 2 days after the platelet count normalizes. If plasma exchange is unavailable, infusions of fresh frozen plasma can be given; however, these are associated with an inferior outcome compared with plasma exchange. Infection in patients with impaired immunity Patients with a variety of haematological diseases are immunocompromised as a result both of their underlying disease and the treatment required for the condition. Impaired immunity to infection may be the result of neutropenia, lymphocytopenia, hypogammaglobulinaemia or a combination of these abnormalities (Table 14. A number of haematology patients will be severely neutropenic following either inpatient or outpatient aggressive chemotherapy Table 14. Less commonly Organisms Streptococcus pneumoniae (60%), Haemophilus influenzae type b, Neisseria meningitidis Escherichia coli, malaria, babesiosis, Capnocytophaga canimorsus Haematological Emergencies 83 regimens or as a result of their underlying disease. It is essential that these patients are counselled and supplied with contact numbers and that they understand the urgent need for hospital admission if they become unwell and/or develop a fever. Many of these patients have indwelling tunnelled intravenous catheters, and line-related infections with Gram-positive organisms are common. Removal of the tunnelled catheter may be necessary for severe or persistent line-associated infections. Frequent courses of antibiotics may be required, but intravenous immunoglobulins are rarely used, owing to the limited evidence of their efficacy. Recurrent and severe herpes zoster infections may also occur, and prompt treatment with aciclovir should be given at the first suspicion of herpetic lesions developing. Patients with either functional or anatomical asplenia are at an increased risk of infection with encapsulated organisms, notably Streptococcus pneumoniae. Counselling regarding the need for prompt treatment with antibiotics in the event of a fever Box 14. Guidelines on the diagnosis and management of the thrombotic microangiopathic anaemias. Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Neurological aspects of monoclonal gammopathy of undetermined significance, multiple myeloma, and related disorders. Fevers of this type are also seen in other immunocompromised patients, such as those with neutropenia. Guidelines for the use of fresh frozen plasma and cryoprecipitate and cryosupernatant. The Effective Prevention and Management of Common Complications of Induction Chemotherapy in Haematological Malignancy. Plasmapheresis for hyperviscosity syndrome in macroglobulinaemia Waldenstrom and multiple myeloma; influence on blood rheology and the microcirculation. Other "biological "therapies such as anti-cancer vaccines and viral vectors for gene therapy are entering clinical study and are likely to follow suit · "Targeted" drug therapies based on known molecular aberrations will play an increasing role this chapter assesses the impact of advances in science and technology on the practice of haematology and attempts to predict how haematology might change further over the next 10­15 years (Box 15. The major advances in scientific thought and technological development that have already changed the practice of modern haematology are likely to affect both laboratory diagnosis and treatment in the future. Another very exciting development that will ultimately affect the practice of haematology is the discovery of the plasticity of postnatal stem cells. The identification of postnatal progenitors that can, ex vivo, be expanded and differentiated into many different cell types, ultimately may pave the way for the treatment of solid organ tissue damage as well as correcting genetic disorders of many kinds. They are obtained relatively easily, making them an attractive strategy for clinical application. Although the debate about the ethical implications of the use of embryonic stem cells continues in many countries, postnatal stem cells offer a realistic and non-controversial alternative. The chapter begins with an introduction to genomics and gene therapy, both of which are likely to have a role in most areas of haematological practice in the future. Three specific areas of haematology ­ haemoglobinopathy, haemophilia, and haematological malignancy ­ are then examined, in each of which important innovations could be expected to change clinical practice. Both diagnostically and therapeutically, the identification of the molecular pathology of the underlying disorder will continue to steer the future. The ability to make more accurate diagnoses in haematology is only just beginning to result in improved treatments. Careful clinical studies with well designed correlative science that aims to ask and answer specific questions should remain the basis on which novel developments make their impact on routine practice. Gene therapy the term gene therapy is applied to any manoeuvre in which genes or genetically modified cells are introduced into a patient for therapeutic benefit. Successful gene therapy depends on the availability of reliable methods for delivering a gene into selected target cells and subsequently ensuring the regulation of gene expression. Haematological cells are readily accessible for manipulation and so can be genetically modified outside the body and reinfused. The aim in the future perhaps might be to modify the target cells without first removing them from the patient. A vector must be able to access the cells to be transduced and bind and penetrate the membrane of the target cell. Gene expression must be at a high enough level and sufficiently regulated for clinical benefit. For gene therapy applications, where it is crucial to achieve gene expression in the progeny of the target (modified) cells, it is important to use a vector that stably inserts its genes into the chromosome of the host cell, and retrovirus vectors are the most suitable for this purpose. For direct in vivo gene delivery, vector attachment to a specific target cell is a vital additional requirement. The former have evolved natural mechanisms to deliver genomes into cells, making them ideal vehicles for use in gene therapy. Considerable work in developing viral and non-viral vector systems is underway to try to achieve the steps outlined above. To date, most successful gene therapy applications have employed retroviral vectors (Table 15. This is crucial for achieving adequate gene expression in the progeny of the target cells. Significant immune reconstitution was seen in the majority of patients treated with this approach ­ a major success. However, three cases of T-cell leukaemia in children treated by this method were reported. What remains unclear for future studies is to what extent retroviral vectors per se are responsible for mutagenic events. Particular risks in these patients that contributed to the insertional mutagenesis included the high transduction rate of the vector, the young age of the patients and the strong selective advantage given to transduced cells by the correction of the genetic defect. Despite these problems, the great potential for gene transfer technologies to treat and cure genetic diseases continues to spur interest in this field. Recently, the number of genes in the human genome has been estimated at being between 30 000 and 40 000, many less than previously thought. The function of most of these genes currently remains unknown, although it is likely that this will not always be the case. A huge amount of data can be gathered in this manner, but to turn this into interpretable information requires considerable computing capacity. The processing and interpretation of the data obtained is known as bioinformatics. The best characterized clinical application of gene profiling is in patients with diffuse large Bcell and follicular lymphomas. In recent years, several large scale studies involving microarray-based gene expression profiling have identified novel prognostic subgroups within each of these lymphoma types. Studies of gene expression can therefore provide a molecular predictor of survival that may be used to inform treatment. In addition, such profiles elucidate the underlying biology of diseases as well as yielding information about the function of unidentified genes. For example, in patients with follicular lymphoma, gene signatures that predict length of survival were found to belong to cells of the immune system. This finding illustrates the importance of immune responses in determining the fate of patients with malignant disorders. The future is likely to see further characterization of these molecules in the diagnoses and treatment of leukaemias. Proteomics, the systematic study of all the proteins in a cell, tissue or organ, may ultimately be more useful than genomics. However, the technical hurdles are much greater, not least because of the vast number and complexity of the proteins to be studied. Improved methods for gel separation of proteins and improved image analysis are likely to make study of the proteome a legitimate goal. Haemoglobinopathies the identification of the precise mutations associated with many forms of hereditary anaemias will allow routine characterization by nucleic acid sequence analysis, facilitating the use of disease-specific diagnostic tests based on polymerase chain reaction. This will provide more precise prognostic information for affected individuals as well as accurate identification of affected embryos. As reliable prenatal diagnosis at an early stage will be available, so will an increasing range of prenatal treatment options. In addition, gene therapy for these disorders could provide another potentially curative strategy, although the genetic correction of hereditary anaemias still presents complex challenges.

Myocardial Ischemia Rhythm: Usually regular but may show atrial and/or ventricular arrhythmias muscle relaxant gel india azathioprine 50 mg order visa. Note: Intraoperative ischemia usually is seen in the presence of "normal" vital signs muscle relaxants quizlet 50 mg azathioprine order with mastercard. Verapamil muscle relaxant antidote buy online azathioprine, quinidine muscle relaxant rub buy azathioprine australia, and amiodarone cause an increase in serum digitalis concentration muscle relaxant drugs over the counter azathioprine 50 mg buy without a prescription. Carotid sinus massage, or other vagal maneuvers, may terminate rhythm or decrease heart rate. May present as electrical alternans; thus, pericardial effusion should be ruled out. Sinus tachycardia may respond to vagal maneuvers but reappears as soon as vagal stimulus is removed. Torsades de Pointes Rate: 150­250 beats/min Rhythm: No atrial component seen; ventricular rhythm regular or irregular. Ventricular Tachycardia Rate: 100­250 beats/min Rhythm: No atrial component seen; ventricular rhythm irregular or regular. Sinus node dysfunction1 · Patients with documented symptomatic bradycardia or chronotropic incompetence · Patients with bradycardia induced by essential medical regimen · Patients with syncopal episodes and induced sinus bradycardia or pauses on electrophysiologic studies · Patients with symptoms and heart rate less than 40 bpm 2. Cardiac transplantation patients who develop persistent inappropriate bradycardia 7. Changes in lead parameters: · Atrial mode switching · Inappropriate ventricular sensing 4297 4. Because a minority of models do not respond to magnet application in the fashion described above, it is always recommended to contact the manufacturer and confirm the response to magnet for the specific model one is dealing with. Activating the electrocautery in the area of the generator, even if the active electrode is not touching the patient, will cause interference. Anesthesia Device Services In the last few years, perioperative management of rhythm devices has 4301 become a more active focus of the Surgery and Anesthesia Departments in different institutions across the country. This is due to the increasing number of patients that present for surgery with one of these devices in place, posing real scheduling and management challenges, with the most concerning issue being scheduling delay. However, it is conceivable that in the future this type of service will become an integral part of the perioperative surgical home, particularly in high volume centers where the scheduling delays have a serious impact. Biventricular pacing is initiated for patients with intraventricular conduction lesions and dyssynchrony of contraction. Rate: program to obtain the best improvement in cardiac output and improvement in mixed venous saturation and arterial blood pressure. Speckle-tracking, 3D echocardiography, M-mode definition of septal to wall motion delay, color Doppler tissue imaging, and analysis of segmental velocity are used to characterize ventricular dyssynchrony. Assessment and management of patients with pacemakers and implantable cardioverter defibrillators. Safety and efficacy of radiofrequency energy catheter ablation of atrial fibrillation in patients with pacemakers and implantable cardiac defibrillators. Radiotherapy-induced malfunction in contemporary cardiovascular implantable electronic devices: clinical incidence and predictors. Radiofrequency scanning for retained surgical items can cause electromagnetic interference and pacing inhibition if an asynchronous pacing mode is not applied. Case report: use caution when applying magnets to pacemakers or defibrillators for surgery. Initial experience of an anesthesiology-based service for perioperative management of pacemakers and implantable cardioverter defibrillators. Optimized temporary biventricular pacing acutely improves intraoperative cardiac output after weaning from cardiopulmonary bypass: a substudy of a randomized clinical trial. These standards may be exceeded at any time based on the judgment of the responsible anesthesiologist. They are subject to revision from time to time, as warranted by the evolution of technology and practice. They apply to all general anesthetics, regional anesthetics, and monitored anesthesia care. In certain rare or unusual circumstances, (1) some of these methods of monitoring may be clinically impractical, and (2) appropriate use of the described monitoring methods may fail to detect untoward clinical developments. Objective Because of the rapid changes in patient status during anesthesia, qualified 4309 anesthesia personnel shall be continuously present to monitor the patient and provide anesthesia care. In the event there is a direct known hazard, for example, radiation, to the anesthesia personnel which might require intermittent remote observation of the patient, some provision for monitoring the patient must be made. Inspired gas: During every administration of general anesthesia using an anesthesia machine, the concentration of oxygen in the patient breathing system shall be measured by an oxygen analyzer with a low oxygen concentration limit alarm in use. When the pulse oximeter is utilized, the variable pitch pulse tone and the low threshold alarm shall be audible to the anesthesiologist or the anesthesia care team personnel. Ventilation Objective To ensure adequate ventilation of the patient during all anesthetics. Qualitative clinical signs such as chest excursion, observation of the reservoir breathing bag, and auscultation of breath sounds are useful. Continual monitoring for the presence of expired carbon dioxide shall be performed unless invalidated by the nature of the patient, procedure, or equipment. Continual end-tidal carbon dioxide analysis, in use from the time of endotracheal tube/laryngeal mask placement, until extubation/removal or initiating transfer to a postoperative care location, shall be performed using a quantitative method such as capnography, capnometry, or mass spectroscopy. During regional anesthesia (with no sedation) or local anesthesia (with no sedation), the adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs. Every patient receiving anesthesia shall have the electrocardiogram continuously displayed from the beginning of anesthesia until preparing to leave the anesthetizing location. Every patient receiving anesthesia shall have arterial blood pressure 4311 and heart rate determined and evaluated at least every 5 minutes. Methods Every patient receiving anesthesia shall have temperature monitored when clinically significant changes in body temperature are intended, anticipated, or suspected. Although cognitive function and physical coordination may be impaired, airway reflexes, and ventilatory and cardiovascular functions are unaffected. No interventions are required to maintain a patent airway, and spontaneous ventilation is adequate. Individuals administering Moderate Sedation/Analgesia (Conscious Sedation) should be able to rescue patients who enter a state of Deep Sedation/Analgesia, while those administering Deep Sedation/Analgesia should be able to rescue patients who enter a state of General Anesthesia. An anesthesiologist shall be responsible for determining the medical status of the patient and developing a plan of anesthesia care. The anesthesiologist, before the delivery of anesthesia care, is responsible for: 4313 1. Discuss the medical history, including previous anesthetic experiences and medical therapy. These standards may be exceeded based on the judgment of the responsible anesthesiologist. They are intended to encourage quality patient care, but cannot guarantee any specific patient outcome. They are subject to revision from time to time as warranted by the evolution of technology and practice. Particular attention should be given to monitoring oxygenation, ventilation, circulation, level of consciousness, and temperature. When discharge criteria are used, they must be approved by the 4315 Department of Anesthesiology and the medical staff. They may vary depending upon whether the patient is discharged to a hospital room, to the Intensive Care Unit, to a short stay unit or home. The name of the physician accepting responsibility for discharge shall be noted on the record. Practice advisory for the Prevention and Management of Operating Room Fires: a report by the American Society of Anesthesiologists Task Force on Operating Room Fires. Monitored anesthesia care includes all aspects of anesthesia care-a preprocedure visit, intraprocedure care, and postprocedure anesthesia management. During monitored anesthesia care, the anesthesiologist provides or medically directs a number of specific services, including but not limited to: · Diagnosis and treatment of clinical problems that occur during the procedure · Support of vital functions · Administration of sedatives, analgesics, hypnotics, anesthetic agents, or other medications as necessary for patient safety · Psychological support and physical comfort · Provision of other medical services as needed to complete the procedure safely. Monitored anesthesia care is a physician service provided to an individual patient. It should be subject to the same level of payment as general or regional anesthesia. Physicians providing moderate sedation must be qualified to recognize "deep" sedation, manage its consequences and adjust the level of sedation to a "moderate" or lesser level. This physician service can be distinguished from Moderate Sedation in several ways. Like all anesthesia services, Monitored Anesthesia Care includes an array of postprocedure responsibilities beyond the expectations of practitioners providing Moderate Sedation, including assuring a return to full 4320 consciousness, relief of pain, management of adverse physiological responses or side effects from medications administered during the procedure, as well as the diagnosis and treatment of co-existing medical problems. Monitored Anesthesia Care allows for the safe administration of a maximal depth of sedation in excess of that provided during Moderate Sedation. In situations where the procedure is more invasive or when the patient is especially fragile, optimizing sedation level is necessary to achieve ideal procedural conditions. In summary, Monitored Anesthesia Care is a physician service that is clearly distinct from Moderate Sedation due to the expectations and qualifications of the provider who must be able to utilize all anesthesia resources to support life and to provide patient comfort and safety during a diagnostic or therapeutic procedure. Prior to procedures requiring anesthetic care, any existing directives to limit the use of resuscitation procedures (that is, do-notresuscitate orders and/or advance directives) should, when possible, be reviewed with the patient or designated surrogate. Full Attempt at Resuscitation: the patient or designated surrogate may request the full suspension of existing directives during the anesthetic and immediate postoperative period, thereby consenting to the use of any resuscitation procedures that may be appropriate to treat clinical events that occur during this time. Limited Attempt at Resuscitation Defined With Regard to Specific Procedures: the patient or designated surrogate may elect to continue to refuse certain specific resuscitation procedures. The anesthesiologist should inform the patient or designated surrogate about which procedures are (1) essential to the success of the anesthesia and the proposed procedure, and (2) which procedures are not essential and may be refused. For example, some patients may want full resuscitation procedures to be used to manage adverse clinical events that are believed to be quickly and easily reversible, but to refrain from treatment for conditions that are likely to result in permanent sequelae, such as neurologic impairment or unwanted dependence upon life-sustaining technology. In cases where the patient or designated surrogate requests that the anesthesiologist use clinical judgment in determining which resuscitation procedures are appropriate, the anesthesiologist should document the discussion with particular attention to the stated goals and values of the patient. Plans for postoperative/postprocedural care should indicate if or 4322 when the original, pre-existent directive to limit the use of resuscitation procedures will be reinstated. This occurs when the patient leaves the postanesthesia care unit or when the patient has recovered from the acute effects of anesthesia and surgery/procedure. It is important to discuss and document whether there are to be any exceptions to the injunction(s) against intervention should there occur a specific recognized complication of the surgery/procedure or anesthesia. Concurrence on these issues by the primary physician (if not the surgeon/proceduralist of record), the surgeon/proceduralist and the anesthesiologist is desirable. Hospital staff should be made aware of the proceedings of these discussions and the motivations for them. Modification of these guidelines may be appropriate when they conflict with local standards or policies, and in those emergency situations involving patients lacking decision-making capacity whose intentions have not been previously expressed. Examples of clear liquids include water, fruit juices without pulp, 4324 carbonated beverages, clear tea, and black coffee. Because nonhuman milk is similar to solids in gastric emptying time, the amount ingested must be considered when determining an appropriate fasting period. Meals that include fried or fatty foods or meat may prolong gastric emptying time. Both the amount and type of food ingested must be considered when determining an appropriate fasting period. Summary of Pharmacologic Recommendations *Note that "continual" is defined as "repeated regularly and frequently in steady rapid succession" whereas "continuous" means "prolonged without any interruption at any time. The qualified practitioner corrects adverse physiologic consequences of the deeper-than-intended level of sedation (such as hypoventilation, hypoxia and hypotension) and returns the patient to the originally intended level of sedation. Further research is required to confirm the potential clinical applicability of these imaging modalities [9]. The latter has been defined as a drop of at least a 50 cm/s from the maximum diastolic velocity but is often assessed subjectively [10]. In the first trimester, the uterine artery Doppler waveform commonly demonstrates an early diastolic notch (46­64% of normal gestations) and low end-diastolic velocities [11]. This phenomenon is secondary to a fall in resistance in uterine vessels following trophoblastic invasion. Abnormal maternal vascular tone is associated with persistent early diastolic notching in the second trimester. Reference ranges for uterine artery Doppler parameters have been established in various populations [13­17] using the techniques described below. Using B-mode imaging, set the field depth to encompass the globe and the retro-orbital space, with the focus set to the latter. The technique for Doppler interrogation of the ophthalmic artery was originally described by Erickson et al. Using color Doppler, identify the ophthalmic artery by its direction of flow (toward the probe) and pulsatility. Ophthalmic artery Doppler analysis: A window into the cerebrovasculature of women with preeclampsia. Apply pulsed wave Doppler, with the sample volume placed around 15 mm behind the optic disc, medial to the optic nerve; the sample volume should be 2 mm in length. Keep the insonation angle at <20°, and set the high-pass filter to its minimum value. Standard Doppler indices may be calculated automatically by the ultrasound machine, although the peak ratio will require manual measurement of the first diastolic peak velocity. Measurements have been shown not to differ between the right and left eyes, validating unilateral assessment [20]. Place electronic calipers across the optic nerve sheath 3 mm behind the globe, perpendicular to the optic 4 Stefan C. Optic nerve ultrasound for the detection of elevated intracranial pressure in the hypertensive patient. Assess the diameter in two planes-transverse and sagittal, the latter requiring rotation of the probe by 90°. The average of the two measurements represents the mean optic nerve sheath diameter if one eye is assessed, whereas if both eyes are examined, the four measurements may be averaged for a single mean sheath diameter.

There are two randomized muscle relaxant pediatrics 50 mg azathioprine purchase with visa, blinded spasms of the heart azathioprine 50 mg order visa, placebocontrolled clinical trials in shock-resistant cardiac arrest victims demonstrating improved survival to hospital with amiodarone treatment spasms upper right abdomen best 50 mg azathioprine, although there was no difference in survival to discharge spasms under left rib purchase azathioprine with a mastercard. Consequently muscle relaxant pregnancy category azathioprine 50 mg buy on line, defibrillation should not be withheld or delayed to establish intravenous access or to administer drugs. In cardiac arrest, amiodarone is initially administered as a 300-mg rapid infusion. Supplemental infusions of 150 mg can be repeated as necessary for recurrent or resistant dysrhythmias to a 4187 maximum total daily dose of 2 g. It is an alternative therapy in refractory fibrillation if amiodarone is not available. Excessive parasympathetic tone probably contributes little to these rhythms during cardiac arrest in adults. Even in children, it is doubtful that parasympathetic tone plays a significant role during most arrests. However, routine use of atropine during cardiac arrest with these rhythms is unlikely to have benefit and is no longer recommended. Use of sodium bicarbonate during resuscitation has been based on the theoretical considerations that acidosis lowers fibrillation threshold and impairs the physiologic response to catecholamines. But most studies have failed to demonstrate improved success of defibrillation or resuscitation with the use of bicarbonate. As measured by blood lactate or base deficit, acidosis does not become severe for 15 or 20 minutes of the cardiac arrest. In the past, metabolic alkalosis, hypernatremia, and hyperosmolarity were common after administration of bicarbonate during resuscitation attempts. Use of clinically relevant doses causes no change in spinal fluid acid­base status or myocardial intracellular pH during bicarbonate administration. Routine use of sodium bicarbonate is not recommended for patients in cardiac arrest. Current practice restricts its use to arrests associated with hyperkalemia, severe pre-existing metabolic acidosis, and tricyclic or phenobarbital overdose. It may be considered for use in protracted resuscitation attempts after other modalities have been instituted and failed. However, dosing of sodium bicarbonate should be guided by blood­gas determination of acid­base status, whenever possible. Calcium With normal cardiovascular physiology, calcium increases myocardial contractility and enhances ventricular automaticity (see Chapter 12). Early animal studies showed moderate success with calcium chloride in asphyxial arrest, although vasopressors were better. Calcium may prove useful if hyperkalemia, hypocalcemia, or calcium channel blocker toxicity is present. When calcium is administered, the chloride salt is recommended because it produces higher and more consistent levels of ionized calcium than other salts. The usual dose is 2 to 4 mg/kg of the 10% solution administered slowly intravenously. Calcium gluconate contains one-third as much molecular calcium as does calcium chloride and requires metabolism of gluconate in the liver. The fibrillating heart has high oxygen consumption, increasing myocardial ischemia and decreasing the time to irreversible cell damage. Initial resuscitation success following out-ofhospital fibrillation and survival to hospital discharge are improved the earlier that defibrillation is accomplished. For this reason, the trace from a second lead or from a different position of paddle electrodes should always be inspected before a decision is made not to defibrillate. Low-amplitude fibrillatory waveforms are less likely to be associated with successful resuscitation and more likely to convert to asystole following defibrillation. Catecholamines with adrenergic activity increase the vigor of fibrillation and the amplitude of the electrical activity, leading to the practice of administering epinephrine to make it "easier" to defibrillate. However, experimental work has shown that manipulation of the electrical pattern with epinephrine does not influence the success of defibrillation or reduce the energy needed for defibrillation. Defibrillators: Energy, Current, and Voltage Defibrillators derive power from a line source of alternating current or an integral battery. The typical defibrillator consists of a variable transformer that stores direct current in a capacitor, a switch to charge the capacitor, and discharge switches to complete the circuit from capacitor to electrodes. Defibrillators are classified by the current waveform delivered: monophasic (current flows in one direction between electrodes) or biphasic (current reverses direction between electrodes during the shock). Older defibrillators used a monophasic damped half-sinusoid or a monophasic truncated exponential waveform. Unfortunately, rhythm analysis can require up to 90 seconds, during which chest compressions are not being given. Some defibrillators measure transthoracic impedance prior to the shock by passing a low-voltage current through the chest during the charge cycle. However, the output of defibrillators is indicated in energy units (joules or wattseconds), not current (amperes). The relationships among energy, current, and impedance (resistance) are given by the following equations (standard units are indicated): From these equations, it can be determined that as the impedance between the paddle electrodes increases, the delivered energy will be reduced. Because internal resistance is low, the primary determinant of delivered energy will be transthoracic impedance. Even at a constant delivered energy, equation 58-4 indicates that the delivered current (the critical determinant of defibrillation) will be reduced as impedance increases. At high impedance and relatively low energy levels, current could be too low for defibrillation. Transthoracic Impedance Transthoracic impedance has been measured between 15 and 143 ohms in human defibrillation136 (see Chapter 12). Many of the important factors in minimizing transthoracic impedance are under the control of the rescuers. Resistance decreases with increasing electrode size, and studies suggest that optimal paddle size may be 13 cm in diameter. Gel pads, electrode paste, or self-adhesive defibrillation or monitor pads specifically designed to conduct electricity in the defibrillation setting must be used. Transthoracic impedance is slightly, but significantly, higher during inspiration than during exhalation. Firm paddle pressure of at least 11 kg reduces resistance by improving paddle-to-skin contact and by expelling air from the lungs. However, if energy is too low, the delivered current may be insufficient for defibrillation, especially when transthoracic impedance is high. There appears to be little risk of significant myocardial injury with currently recommended energy levels. Older studies using monophasic waveform defibrillators found a general relationship between body size and energy requirements for defibrillation. Neither waveform has been associated with better return of spontaneous circulation or survival. With monophasic defibrillators, a single shock of 360 J should be given with immediate resumption of chest compressions. Most manual biphasic devices display the effective dose range and the user should select that dose. If the effective dose for a manual biphasic device is unknown, a dose of 200 J may be selected. This dose may not be optimal but falls within the effective dose range of nearly all biphasic devices. As with the monophasic devices, a single shock should be delivered with immediate resumption of chest compressions. The algorithms for approaching the patient with cardiac arrest published in the guidelines are familiar to all physicians and are reproduced in this chapter. A continuous quality improvement model may be more relevant to improved outcomes than the randomized control trial. In addition, there is increasing awareness that the single approach to two pathophysiologically distinct entities (respiratory arrest and cardiac arrest) may not be optimal care for either. In the former, arrest occurs because of hypoxemia, and reoxygenating the blood by effective ventilation is mandatory for successful resuscitation. In the latter, arrest occurs because of cardiac dysrhythmia, usually with normal oxygenation, and attempts at ventilation during resuscitation, in fact, may be harmful. The electrical phase occurs during the first 4 to 5 minutes of the arrest, and early defibrillation is critical for success during this time. The hemodynamic phase follows for the next 10 to 15 minutes, when perfusing the myocardium and brain with oxygenated blood is critical. This is followed by what has been called the metabolic phase, when the ischemic injury to the heart is so great that it is not clear what interventions will be successful. However, in the usual out-of-hospital rescue with emergency medical technicians or paramedics doing the defibrillation, a rapid response is to apply the first shock in 6 to 7 minutes, and the time to first shock frequently is more than 10 minutes. Therefore, the most important intervention during the hemodynamic phase of cardiac arrest is producing coronary perfusion with chest compressions before any attempt to defibrillate. In the absence of prompt defibrillation, the most important intervention for neurologically normal survival from cardiac arrest is restoration and maintenance of cerebral and myocardial blood flow. Because perfusion pressures generated by chest compressions are quite low compared with the intact circulation, any interruption of chest compressions markedly reduces the chances for neurologically normal survival. Therefore, any intervention that interrupts chest compressions is strongly discouraged. Early studies in anesthetized, paralyzed humans suggested that the airway would not remain open in the unconscious,6,7 leading to the teaching that airway control and artificial ventilation must accompany chest compressions. However, there are considerable data to suggest that eliminating mouth-to-mouth ventilation early in the resuscitation of witnessed fibrillatory cardiac arrest is not detrimental to outcome and may improve survival. When the 30:2 ratio with a more realistic 16-second pause for ventilations is compared with continuous chest compressions without ventilation in the animal model, the 24-hour neurologically normal survival is only 42% in the 30:2 group compared with 70% in the continuous compressions group. The adverse hemodynamic consequences of interrupting chest compressions have been well documented. Several compressions are necessary before perfusion pressures return to the levels obtained before compressions were stopped. But it is also relevant for the many other interruptions that occur during resuscitation: pulse checks, rhythm analysis, charging the defibrillator, stacked shocks, intubation, patient assessment, and intravenous line placement. Recent reports have documented that paramedics spend only about half the time during a resuscitation doing chest compressions, mostly because they are following the standard guidelines. Initial airway management may consist of insertion of an oropharyngeal airway and providing oxygen by mask with rescue breaths, assisted ventilation or intubation delayed until return of spontaneous circulation or until at least three cycles of compressions­rhythm analysis­shock are complete. If there are time and resources for airway management, ventilation and intubation are encouraged to take place while chest compressions continue. Once ventilation begins, rescuers must be aware of the potentially deleterious effects of positive-pressure ventilation. These effects are amplified by the fact that physicians and paramedics often 4198 ventilate at rates that are many times the recommended 10 breaths per minute, even after extensive retraining. The interruption caused by stacked defibrillatory shocks was discussed previously. Immediately restarting chest compressions after defibrillation to provide coronary perfusion nearly always results in reversion to a perfusing rhythm. In rural Rock and Walworth counties in Wisconsin, in the 3 years preceding a change, there were 92 witnessed out-ofhospital adult cardiac arrests with an initially shockable rhythm; 18 of these victims survived and 14 (15%) were neurologically intact. In the first 3 years of applying a minimal-interruption approach in these counties, there were 89 witnessed out-of-hospital cardiac arrests; 42 (47%) of these patients survived and 35 (39%) were neurologically intact. These highly statistically significant results are encouraging in that they indicate a significant improvement in outcome from sudden cardiac death is possible. However, the consequences of myocardial and cerebral ischemia are the same as for the adult, and the basic approach to the unresponsive victim is similar. The specific anatomic and physiologic considerations necessary for the child will be familiar to anesthesiologists. The special circumstance of neonatal resuscitation is discussed in Chapters 41 and 42. The problem of airway management in the infant is well known to the anesthesiologist. Effective ventilation is especially critical because respiratory problems are frequently the cause for arrest. Mouth-to-mouth or mouth-tonose and mouth (for infants) can be used as well as bag-valve-mask devices until intubation is possible. Cardiac compression in the infant is provided with two fingers on the midsternum or by encircling the chest with the hands and using the thumbs to provide compression. For both infants and 4200 children, compressions should be at least one-third the depth of the chest at a rate of 100 to 120/min. For a single rescuer, a 30:2 compression-toventilation ratio should be used and with two or more rescuers a 15:2 ratio is recommended. Although defibrillation is less frequently necessary in children, the same principles apply as in the adult. However, the recommended starting energy is 2 J/kg (monophasic or biphasic), which is doubled if defibrillation is unsuccessful. Considerations for drug administration are the same as for the adult, except that the interosseous route in the anterior tibia is a particularly attractive option in small children. Drug therapy is similar to that of the adult but plays a larger role because electrical therapy is less often needed (Table 58-3). Table 58-3 Medications for Pediatric Resuscitation Postresuscitation Care the major factors contributing to mortality following successful resuscitation are progression of the primary disease and cerebral damage suffered as a result of the arrest. For optimal outcome, successful restoration of spontaneous circulation must be followed 4203 by correction of reversible causes of arrest, including immediate coronary reperfusion and aggressive supportive care. Any cardiac arrest, even of brief duration, causes a generalized decrease in myocardial function similar to the regional hypokinesis seen following periods of regional ischemia. This is usually referred to as global myocardial stunning and can be mitigated with inotropic agents, if necessary. Active management following resuscitation appears to mitigate postischemic brain damage and improve neurologic outcomes.

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