By X. Kelvin. California State University, San Marcos.
Ganciclovir prophylaxis is used for lung buy genuine amoxil antibiotic resistance evolution, heart–lung purchase amoxil 500mg on line virus and fever, and heart transplant recipients as well  best 250 mg amoxil antibiotics that treat strep throat, but data on surveillance, preemptive therapy, and efficacy in such recipients are limited. In profoundly immunosuppressed patients, they may cause widespread disease, including hepatitis, encephalitis, and pneumonitis. The diagnosis is established by identification of the virus by immunofluorescent monoclonal antibody staining or by Tzanck smear. Treatment consists of acyclovir; most epidermal lesions respond to oral therapy, but any evidence of disseminated disease requires high-dose intravenous acyclovir and minimization of immunosuppression. The most common manifestations include the typical mononucleosis-type syndrome, pneumonitis, and hepatitis. Pediatric transplant patients are routinely innoculated with the varicella vaccine, which has markedly reduced this type of disease; the vaccine is recommended pretransplant for all pediatric and nonimmunosuppressed transplant candidates. Up to 25% of hepatitis C–positive transplant recipients accelerate to cirrhosis within 5 to 10 years posttransplant, likely related to immunosuppressive therapy and rejection . A very effective interferon-free regimen, which obtains high sustained viral response within 8 to 12 weeks of therapy, has proved effective in managing hepatitis C, although the cost is considered prohibitive, with barriers including insurance denials; however, it is much cheaper than liver transplantation. Reactivation takes place when the host’s immune system is compromised, such as during pregnancy or posttransplant immunosuppression. The diagnosis is made by detecting free viral particles in the urine, blood, or intranuclear viral inclusion- bearing cells (decoy cells) in urine cytology specimens. Human papilloma viruses may cause disease through the development of tissue-specific growth, leading to benign or malignant processes, including cervical cancer, cancer of the vulva and perineum, condyloma acuminatum, laryngeal polyposis, and nonmelanotic skin cancer (vide infra). Respiratory syncytial virus may produce a fulminant pneumonia in both adult and pediatric transplant recipients. Parasitic Infections Numerous common parasitic infections are seen in immunosuppressed solid-organ transplant recipients. It is seen late posttransplant, whereas a brain abscess in the early posttransplant period is more likely to be fungal . The Israel Penn International Transplant Tumor Registry initiated and has maintained an extensive data collection that tracks the epidemiology of tumors in transplant recipients . The increased incidence of malignancy is multifactorial, probably due to a combination of the activation of latent viruses with oncogenic potential, the direct oncogenic effect of immunosuppressive drugs such as cyclosporine, and, perhaps, environmental factors . Strong but indirect evidence points to the loss of immunologic surveillance as a mechanism of increased oncogenesis. Of those neoplasms, lung cancer appears to occur at the same frequency as in the general population; the other neoplasms occur at increased incidence in solid-organ transplant recipients. These late occurring neoplasms appear to be related to patient age, duration, and intensity of immunosuppression, and type of graft than to the more typical risk factors seen in early-onset disease. Weight loss, diarrhea, and upper respiratory infection are common symptoms; some, but not all, patients have lymphadenopathy. Similarly, peripheral cytology is not helpful in making the diagnosis and molecular techniques need to be employed . Ordinarily, immunosuppression is reduced to the barest minimum, and specific therapy is directed at the neoplasm. Therapeutic options include intrathecal administration of interferon-α and anti–B-cell antibody therapy in addition to local radiotherapy, but the prognosis remains guarded . Skin Cancer Nonmelanotic skin cancers are the most common neoplasms associated with transplantation and immunosuppression. Often-quoted studies show a prevalence of 66% in transplant recipients in Australia after 24 years of surveillance  and 40% after 20 years in the Netherlands . Those figures correlate to a 4- to 21-fold increase in prevalence in transplant recipients, as compared with the immunocompetent population, with synergistic increases seen in the areas of highest sunlight exposure in countries such as Australia . Many recipients develop multiple lesions; the transplant patients are generally younger when compared with members of general population. Even nonmelanotic squamous cell carcinomas behave more aggressively in transplant recipients, with lymph node metastasis and a 6% mortality rate due to disseminated disease . Solid-organ transplant recipients are instructed to avoid direct exposure to sunlight for any prolonged period of time and to liberally use sunblock. Clearly, close dermatologic counseling, education, and follow-up are warranted in this patient population . Immunosuppression should be reduced to the greatest extent possible, after which about 30% to 55% of patients will experience remission. Cervical Cancer the incidence of cervical intraepithelial neoplasia is elevated by 10- to 14- fold in solid-organ transplant recipients and may approach 50% . Cervical carcinoma was seen in 10% of all women with posttransplant cancer in the Transplant Tumor Registry . Close surveillance by pelvic examination and Papanicolaou smear is essential in this population, given the increased incidence of disease. In the posttransplant patient with potentially advanced cervical cancer, there is no standardized approach. Transmitted and Recurrent Malignancy Thankfully the transmissions of malignancy from grafts are not widespread, but when it does occur it is potentially devastating. Case reports have described patients who received grafts that harbored malignant cells, leading to the development of malignancy. Transmission to transplant recipients of renal cell carcinoma, metastatic cancer of the breast or lung, and melanoma has been reported. Nonetheless, some grafts are found to contain foci of neoplasia, which develop into a clinically significant cancer in recipients. This finding emphasizes the need for a thorough examination of donors during organ procurement, particularly considering the present trend toward the use of older donors. Patients with a history of malignancy are clearly at risk for recurrent disease posttransplantation, presumably due to the use of immunosuppression. Data from the Transplant Tumor Registry show a 21% recurrence rate, with the highest rates seen in patients with multiple myeloma (67%), nonmelanotic skin cancer (53%), bladder cancer (29%), soft tissue sarcoma (29%), renal cell cancer (27%), and breast cancer (23%) , and there is a tendency to using organs with small, incidental renal cell carcinoma may be reasonable . Tumors were least likely to recur if more than 5 years had passed between cancer treatment and the transplantation. Liver transplantation to treat patients with primary, well- circumscribed liver tumors represent a special case. In this population, liver tumor size and the number of liver tumors are considered indicative of the likelihood of disease recurrence and patient survival posttransplantation. Adjuvant techniques, such as cryoablation and radiofrequency ablation, to reduce the tumor burden pretransplantation have been used, but currently the data are insufficient to clearly define the ability of adjuvant techniques to reduce posttransplant morbidity and mortality secondary to disease recurrence. Risk factors for recurrence include tumor size >6 cm, number of nodules >5, and vascular invasion per the final pathology report . However, a side effect of the ability of the host immune system to recognize and attack “nonself” tissues is rejection of grafted tissues posttransplantation. That side effect was observed clinically for centuries before Medawar demonstrated that it was an intrinsic property of the host immune system in response to foreign tissue . The exogenous modulation of the host immune system to allow sustained graft function has proceeded along with—and often preceded—our understanding of the physiologic mechanism of rejection and tolerance. The immunologic disparity among members of the same species of mammals that leads to lack of recognition of “self” tissue and to rejection of nonself tissue is based on the differences in cell surface molecules that are expressed. The recognition of nonself tissue occurs via two distinct immunologic pathways: direct and indirect allorecognition.
Furthermore order amoxil canada infection 6 weeks after wisdom tooth removal, the narrow time window for the administration of antibiotics as advocated by the Surviving Sepsis Campaign Guidelines (administration within 3 hours of Emergency Department triage and within 1 hour of severe sepsis/septic shock recognition) is not supported by a meta-analysis of cohort studies that investigated this issue  discount 500 mg amoxil visa antibiotics uti. This section will focus on appropriate antibiotic therapy discount 500mg amoxil mastercard bacteria pseudomonas, hemodynamic management, source control, and adjunctive therapies that may be of potential benefit in patients with severe sepsis and septic shock. Antimicrobial Therapy Empiric intravenous antibiotic therapy should be started as soon as possible after appropriate cultures have been obtained. Although the tight window as suggested by the Surviving Sepsis Campaign is not supported by scientific evidence, common sense would dictate that delaying the administration of antibiotics serves no useful purpose. Initial empiric anti-infective therapy should include one or more drugs that have activity against the likely pathogens and that penetrate into the presumed source of sepsis site. Because the identity of the infecting pathogen(s) and its sensitivity pattern(s) are unknown at the time of initiation of antibiotics, for patients with severe sepsis and septic shock the initial regimen should include two or more antibiotics or an extended spectrum β-lactam antibiotic. A number of studies have demonstrated that appropriate initial antimicrobial therapy, defined as the use of at least one antibiotic active in vitro against the causative bacteria, is associated with a lower mortality when compared with patients receiving initial inappropriate therapy [82,83]. Once a pathogen is isolated, monotherapy is adequate for most infections; this strategy of initiating broad-spectrum cover with two or more antibiotics and then narrowing the spectrum to a single agent when a pathogen is identified is known as “antimicrobial de-escalation” . Antimicrobial de-escalation has been demonstrated to be associated with lower rates of hospital mortality . The indications for continuation of double-antimicrobial therapy include enterococcal infections and severe intra-abdominal infections. In order to rapidly achieve adequate blood and tissue concentrations, antibiotics should be given intravenously, at least initially. With the widespread use of antibiotics, a group of pathogens have emerged that are resistant to multiple antibiotics. The appropriate length of antibiotic treatment for patients with sepsis has not been well established, with marked variation between and within different countries and healthcare settings, independent of factors such as disease severity . In this study, there were no differences for any of the outcomes studied between the two dosing strategies. Hemodynamic Support On November 8, 2001, Emanuel Rivers and collaborators published a study entitled “Early Goal Directed Therapy in the treatment of severe sepsis and septic shock,” in which they compared two protocols for the early resuscitation of patients with severe sepsis and septic shock (for 6 hours in the Emergency Department) . The study, which enrolled 288 patients (252 were excluded after the fact), reported a 28-day mortality of 49. Within a short time, this small (severely underpowered), unblinded, single-center study came to be considered the standard of care around the world and formed the basis of the 6-hour resuscitation bundle of the 2004, 2008, and 2012 Surviving Sepsis Campaign Bundles [50,94,95]. This premise is flawed as bioenergetic failure and cellular hypoxia are likely only preterminal events in patients with septic shock [102,103]. Patients with sepsis should be managed by a thoughtful individualized approach based on an understanding of human physiology, the pathophysiologic changes that occur with sepsis, the patients’ comorbidities, and the best clinical evidence. In these highly vulnerable patients, more intensive treatment may promote the chances of unwanted adverse effects and hence iatrogenic injury . Current teaching suggests that aggressive fluid resuscitation is the best initial approach for the cardiovascular instability of sepsis. There is, however, no human data that large fluid boluses (>30 mL per kg) reliably improves blood pressure, urine output, or end-organ perfusion [109,110]. Multiple studies of diverse populations of patients have demonstrated that only about 50% of hemodynamically unstable patients are fluid responsive [112,113]. This implies that for about 50% of hemodynamically unstable patients, fluid boluses may be harmful . This challenges the “well established” notion in critical care medicine, anesthesiology, and emergency medicine that fluid boluses are the “cornerstone of resuscitation. To make matters worse, the hemodynamic response to fluids in patients with circulatory shock is small and short lived (less than an hour) because most (about 90% to 95%) of the fluid leaks into the tissues [124–127]. Glassford and colleagues performed a systematic review that examined the hemodynamic response of fluid boluses in patients with sepsis . Although having a minimal effect on blood pressure, fluid boluses may cause a fall in effective arterial elastance and systemic vascular resistance, potentiating arterial vasodilatation and the hyperdynamic state characteristic of septic shock [129,130]. These data suggest that the majority of patients with severe sepsis and septic shock are not fluid responders. The hemodynamic changes of the fluid responders are small, short lived, and likely to be clinically insignificant. Furthermore, overaggressive fluid resuscitation will likely have adverse hemodynamic consequences including an increase in cardiac filling pressures, damage to the endothelial glycocalyx, arterial vasodilation, and tissue edema. Consequently, the concept that aggressive fluid resuscitation is the “cornerstone of resuscitation” of patients with severe sepsis and septic shock should be reconsidered [50,94,95,131]. The harmful effects of overaggressive fluid resuscitation on the outcome of sepsis are supported by experimental studies as well as data accumulated from clinical trials [132,133]. Multiple clinical studies have demonstrated an independent association between an increasingly positive fluid balance and increased mortality in patients with sepsis [1,45,134–141]. In this study, 67% of patients had clinical evidence of fluid overload at 24 hours with 48% having evidence of fluid overload at 72 hours. In this randomized study, aggressive fluid loading was associated with a significantly increased risk of death. Nevertheless, despite data suggesting that “aggressive fluid resuscitation” is associated with adverse outcomes and no randomized trials to indicate that this approach improves patient outcomes, the updated Surviving Sepsis Campaign Guidelines, published in April of 2015, mandates the administration of “30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L” within 3 hours of presentation to hospital . In summary, these data support a “conservative” hemodynamically guided fluid resuscitation strategy in patients with severe sepsis and septic shock. From an evolutionary point of view, humans have evolved to deal with hypovolemia and not hypervolemia. Large fluid boluses may counter the live preserving homeostatic mechanisms of unstable critically ill patients, increasing the risk of death . It is likely that many of these patients have super-added dehydration owing to poor oral intake and a delay in seeking medical attention. However, fluids alone will not reverse the hemodynamic instability of patients with more severe sepsis; for these patients, fluids alone are likely to exacerbate the vasodilatory shock and increase the capillary leak and tissue edema. On the basis of these data, the initial resuscitation of patients with septic shock should logically include 500 mL boluses of crystalloid (Ringers Lactate) to a maximum of about 20 mL per kg . The septic patient with an intra-abdominal catastrophe who requires urgent surgical intervention represents one subgroup of patients that may require more aggressive fluid resuscitation. However, overly aggressive fluid resuscitation can result in intra-abdominal hypertension, which is associated with a high risk of complications and death [148,149]. However, normal saline is an unphysiologic solution that is associated with a number of adverse effects. Normal saline causes a hyperchloremic metabolic acidosis [150–153]; it decreases renal blood flow  and increases the risk of renal failure . In patients with sepsis, the use of normal saline as compared with physiologic salt solutions has been associated with an increased risk of death .
Prevention Given the long-term nature of immunosuppression in graft recipients buy amoxil with amex xyrem antibiotics, preventive measures play a critical role in preventing morbidity and mortality buy discount amoxil 500 mg line antibiotics gel for acne. The recommended preventive measures can be categorized by pathogen type: • Bacteria buy cheap amoxil 500mg on-line bacteria 5 letters. In the patient with a documented reduction in IgG level below 400 mg/dL, intravenous IgG may be given to prevent sinus and pulmonary infections resulting from S. If these tests are positive, the patient should be treated with intravenous ganciclovir 5 mg/kg twice daily for 14-21 days or oral valganciclovir 900 mg twice during the first 24 hours for induction, and then 900 mg daily. Antiherpes simplex IgG titers should be measured in all potential recipients before transplantation. Emergent management is required for a) central nervous system symptoms such as headache and confusion— consider Cryptococcus and Listeria. Other transplant patients undergoing high-level immunosuppression should also be considered for prophylaxis. Reactivation of varicella virus can lead to serious morbidity and also requires preventive measures. The recipient and all family members should be vaccinated with the live attenuated vaccine at least 4 weeks before the transplant procedure. Allogeneic bone marrow transplant patients have a high incidence of Candida albicans infection during phase I and should receive oral fluconazole 400 mg daily or posaconazole (200 mg three times daily) for prophylaxis. Throughout the period of immunosuppression, transplant patients are at risk of infection with this organism, and oral trimethoprim–sulfamethoxazole (one double-strength tablet three times weekly, or one single-strength tablet daily) is recommended. Bone marrow recipients with positive IgG titer for herpes simplex virus should receive valacyclovir. Vaccine for varicella virus should be given to patients and household contacts before a transplantation procedure. Allogeneic transplant patients should receive fluconazole or posaconazole to prevent fungal infections. All transplant recipients should receive trimethoprim- sulfamethoxazole to prevent Pneumo-cystis infection. These patients fit into two general categories that predispose them to infections that are usually controlled either by neutrophils or by T cells. Bone marrow or stem cell transplant patients fit into both categories depending on how much time has passed since transplantation. The febrile neutropenic patient can be considered to be a medical emergency requiring empiric antibacterial therapy with one or two broad-spectrum antibiotics. Conversely, the patient with suppression of cell-mediated immunity requires a thorough evaluation, and empiric antibiotic therapy should be avoided unless the cause of the fever is known on presentation. It is advisable that these patients receive care from infectious disease specialists. Outpatient management of these patients can be expected to become increasingly common. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis: An official publication of the Infectious Diseases Society of America. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients. Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalo-virus in solid organ transplant recipients. Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study. Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome. Treatment of febrile neutropenic patients with cancer who require hospitalization: a prospective randomized study comparing imipenem and cefepime. Once daily, oral, outpatient quinolone monotherapy for low-risk cancer patients with fever and neutropenia: a pilot study of 40 patients based on validated risk-prediction rules. Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts. Role of glycopeptides as part of initial empirical treatment of febrile neutropenic patients: a meta-analysis of randomised controlled trials. Infections in patients with febrile neutropenia: epidemiology, microbiology, and risk stratification. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. Use of antibacterial prophylaxis in patients with chemotherapy- induced neutropenia. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Compliance with a critical pathway for the management of febrile neutropenia and impact on clinical outcomes. What are the goals for therapy, and what are the factors that increase the risk of developing resistance? The associated opportunistic infections are often difficult to diagnose and frequently life- threatening. In the sub-Saharan countries, transmission occurs predominantly by heterosexual intercourse, with as many women as men being infected. The problems of North America and Western Europe pale in comparison with those of Africa. Incidence figures are difficult to determine, because most newly acquired infections are not diagnosed. Judging from the number of first positive tests (which may be the result of an infection acquired years earlier), infection rates declined during the 1990s, reaching a plateau around 1998. The chance of acquiring an infection after a needle-stick injury involving infected bodily fluids is about 1 in 300. Most infections occur with sexual exposure, the primary determinant of infectivity being the level of virus in genital secretions. Highest incidence is found in Africa where the virus originated: a) New infections occur at a rate of 2-3 million annually. North America and Europe have lower incidences and prevalences: a) Prevalence in the United States 1. Compared with infection rates for other sexually transmitted diseases (20- 40% after exposure to syphilis or gonorrhea), this risk is quite low. Nonetheless, repeated sexual exposure—as occurs in a serodiscordant couple —entails substantial risk, up to 1% per month.
If additional atropine does not correct the problem buy on line amoxil antibiotics for bladder infection nitrofurantoin, the patient may require judicious use of isoproterenol or pacemaker therapy order 250mg amoxil overnight delivery antibiotics for canine ear infection. The contractile state of the myocardium depends in part on the intracellular concentration of the calcium ion purchase amoxil with a visa antibiotics for acne clindamycin. Transmembrane calcium flux serves an important regulatory function in both active contraction and active relaxation. The use of calcium in cardiac arrest is based on an early report by Kay and Blalock  in which several pediatric cardiac surgical patients were successfully resuscitated, apparently with the aid of calcium. However, several field studies have failed to demonstrate an improvement in survival or neurologic outcome with the use of calcium versus a control . In addition, after standard doses of calcium administered during cardiac arrest, many patients are found to have very high calcium blood levels . This is apparently due to the markedly contracted volume of distribution of the ion in the arrested organism. In addition, calcium has the theoretic disadvantage of facilitating postanoxic tissue damage, especially in the brain and heart. Calcium is indicated only in specific circumstances: calcium channel blocker toxicity, severe hyperkalemia, severe hypocalcemia, arrest after multiple transfusions with citrated blood, fluoride toxicity, and while coming off heart–lung bypass after cardioplegic arrest. It is highly irritating to tissues and must be injected into a large vein with precautions to avoid extravasation. If bicarbonate has been administered through the same line, it must be cleared before introducing the calcium. The following sections focus on the pharmacologic and electric interventions appropriate to various clinical settings common in cardiac arrest. Special Situations Patients who have nearly drowned in cold water may recover after prolonged periods of submersion. Apparently, the hypothermia and bradycardia of the diving reflex may serve to protect against organ damage . The body’s ability to maintain temperature is diminished by alcohol, sedation, antidepressants, neurologic problems, and advanced age. Because of the associated bradycardia and oxygen- sparing effects, prolonged hypothermia and arrest may be tolerated with complete recovery. A longer period may be needed to establish breathlessness and pulselessness because of profound bradycardia and slowed respiratory rate. Electric shock and lightning strike may lead to tetanic spasm of respiratory muscles or convulsion, causing respiratory arrest. More recent evidence suggests that targeting a temperature of 36°C rather than 33°C may offer the same benefit, and has the advantage of less infectious risks and easier use of existing literature to help determine prognosis . Lower cardiac index and hyperglycemia tend to occur more frequently in hypothermic patients, as do infections . Providers considering use of echo to assist in deciding to terminate resuscitative efforts should consider their own skill in performing echocardiography and the overall clinical situation. This requires that a portable ultrasonography machine be placed at the thigh level of the patient as close to the bed as possible with the screen adjusted for optimal image clarity. The operator faces the screen while pressing the probe into the subcostal area in anticipation of the pulse check. Machine setup and operator positioning are not permitted to interrupt chest compressions, as these take absolute priority. When the code team leader alerts the team that a pulse check is required, a team member assumes position contralateral to the ultrasonography machine to prepare to manually check for a pulse in the femoral area, while the ultrasonography operator pre-positions the probe in order to obtain an immediate subcostal long axis view of the heart during the pulse check. When the code leader orders that chest compressions stop for the 5-second pulse check, a skilled scanner can obtain a good quality view of the heart. During chest compressions, it is not possible to obtain any useful images due to the marked translational movement of the heart that occurs during chest compressions (Videos 14. The probe is 0 inserted with 0 transducer rotation to obtain the transgastric short axis view of the left ventricle. Identification of potentially reversible causes of cardiac arrest such as a large pericardial effusion with tamponade, a severely dilated right ventricle with acute cor pulmonale related to a pulmonary embolism, or a heart that is profoundly hypovolemic. This finding is not uncommon, and leads to the consideration that resuscitation efforts should be continued if the clinical situation warrants this. At the tibial insertion site, the operator places the linear vascular probe next to the holding flange of the I/O needle while angling the scanning plane toward the needle tip. The color Doppler map is positioned below the periosteum and 5 cc of sterile saline is injected into the I/O needle. If the needle is well positioned, a color Doppler signal will result deep to the periosteum during the injection (Video 14. A color Doppler signal that is seen superficial to the periosteum indicates misplacement of the needle with the risk of extravasation of adrenergic medication into the subcutaneous compartment. Cardiopulmonary resuscitation: statement by the Ad Hoc Committee on Cardiopulmonary Resuscitation of the Division of Medical Sciences, National Academy of Sciences—National Research Council. Guidelines for the determination of death: report of the medical consultants on the diagnosis of death to the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Holmberg M, Holmberg S, Herlitz J: Effect of bystander cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients in Sweden. Nielsen N, Wetterslev J, Cronberg T, et al: Targeted temperature management at 33°C versus 36°C after cardiac arrest. Nakahara S, Tomio J, Ichikawa M, et al: Association of bystander interventions with neurologically intact survival among patients with bystander-witnessed out-of-hospital cardiac arrest in Japan. Cabrini L, Beccaria P, Landoni G, et al: Impact of impedance threshold devices on cardiopulmonary resuscitation: a systematic review and meta-analysis of randomized controlled studies. Konrad D, Jaderling G, Bell M, et al: Reducing in-hospital cardiac arrests and hospital mortality by introducing a medical emergency team. Rumball C, Macdonald D, Barber P, et al: Endotracheal intubation and esophageal tracheal Combitube insertion by regular ambulance attendants: a comparative trial. De Backer D, Biston P, Devriendt J, et al: Comparison of dopamine and norepinephrine in the treatment of shock. Dorian P, Cass D, Schwartz B, et al: Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. MacMahon S, Collins R, Peto R, et al: Effects of prophylactic lidocaine in suspected acute myocardial infarction: an overview of results from the randomized controlled trials. The Hypothermia After Cardiac Arrest Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. Salen P, Melniker L, Chooljian C, et al: Does the presence or absence of sonographically identified cardiac activity predict resuscitation outcomes of cardiac arrest patients? Kantamineni P, Emani V, Saini A, et al: Cardiopulmonary resuscitation in the hospitalized patient: impact of system-based variables on outcomes in cardiac arrest. Blyth L, Atkinson P, Gadd K, et al: Bedside focused echocardiography as predictor of survival in cardiac arrest patients: a systematic review. Tomruk O, Erdur B, Cetin G, et al: Assessment of cardiac ultrasonography in predicting outcome in adult cardiac arrest. Thanks to the pioneering work of Zoll and Lown in the late 1950s and early 1960s, the use of electric shock gained widespread acceptance.