New horizons (Baltimore, Md.)最新文献

Shock in childhood is most commonly related to injury and blood loss, but hemodynamic compromise is occasionally caused by severe head or spinal injury, tension pneumothorax, myocardial injury, arrhythmias, and sepsis. Regardless of the cause, the initial management of the hypertensive child is establishment of a secure airway, maintenance of ventilation, and initiation of volume replacement via an adequate intravenous catheter. At the present time, crystalloid resuscitation with lactated Ringer's solution and buffering of acidosis with sodium bicarbonate is the standard approach, although in the future hypertonic saline solution may play a role. Hemorrhage may be classified according to the percentage of blood volume lost; losses in excess of 30% of blood volume (class III and IV hemorrhage) usually require administration of packed red blood cells and/or albumin as well. With appropriate management, the typical clinical signs of shock will be reversed and the child will demonstrate improved vital signs, peripheral circulation and sensorium, normalization of body temperature, reversal of metabolic acidosis, and resumption of normal urine output. The more aggressive the approach to resuscitation, the more prompt the patient's response and the more likely morbidity and mortality will be minimized.

Reactive oxygen species (ROS) mediate the fine balance between cellular physiology and pathophysiology. Accordingly it is not surprising that cellular redox homeostasis is disrupted by shock events related to ischemia-reperfusion and inflammation. ROS may initiate as well as amplify the shock cellular insult in a number of ways which include important contributions to inflammation as well as lytic and apoptotic cell death. In addition, ROS in the setting of shock represent important antecedents to cellular proliferation, differentiation, and adaptation by virtue of altered transcription and translation of antioxidant enzymes, stress proteins, and a variety of cytokines. It is likely that an eventual important biochemical therapeutic goal in the setting of shock will involve re-establishing cellular redox homeostasis not only to ensure cellular structural integrity, but also to re-establish normal secondary cellular signal transduction mechanisms.

Septic shock is a complex pathophysiologic state which often leads to multiple organ dysfunction, multiple organ failure, and death. This review summarizes current views on the molecular biology of three aspects of septic shock: recognition of bacterial invasion and induction of the cytokine response; genetic variability among humans and their predispositions toward pathologic inflammatory responses; and the signal transduction mechanisms which account for the transfer of molecular signals from cytokine receptors on the plasma membrane to cytokine-responsive genes in the nucleus. In particular, the review summarizes the pathway involved in tumor necrosis factor signaling through nuclear factor-kappaB, and elucidates the molecular signals involved in inflammatory responses and apoptosis.

Shock in the pediatric population has many preventable causes. Treatment of children in shock will depend on access to health services, training of health personnel, availability of diagnostic procedures, monitoring, and therapeutic measures. Countries will differ among themselves and within themselves in the care provided to children developing shock. In Brazil, the majority of children are cared for in public hospitals, which often lack resources for basic care. Many children in shock do not even reach healthcare services. Investment in training healthcare personnel in a simplified and systematic approach to shock and access to equipped health services are basic to improved outcomes in the treatment of pediatric shock. The Brazilian experience in the treatment of children in shock outside hospital facilities, in the emergency department, and in the ICU is described.

Why some patients develop postoperative surgical wound infection and others do not remains a mystery. There are many risk factors for infection, and mathematical scoring systems are often good predictors of infection; yet, some patients with a plethora of risk factors fail to develop surgical site infections. Even patients with established abdominal infection do not automatically develop wound infection. Early experimental work, now confirmed in the clinical setting, dictates that bacteria must be in the wound to cause infection; the minimal infecting dose will depend on the environmental conditions in the wound. The presence of foreign bodies, trauma, hematoma, etc., will enhance the effect of the inoculum; therefore, surgical debridement and careful surgery are necessary to reinforce the host defenses. Some bacteria, e.g., Staphylococcus aureus and Streptococcus pyogenes, have a greater propensity to cause infection, so extensive infection-control practices are necessary to prevent or contain these pathogens. To minimize the risk of surgical site infection, individual patient risk factors must be identified and modified whenever possible. The patient should be prepared for the operation and appropriate skin antiseptics should be used on the operative site. The patient should be considered for perioperative antibiotic prophylaxis and, if appropriate, bowel preparation should be carried out. Care and attention to the theater operating environment is important, especially for cases in which airborne transmission of bacteria should be controlled, e.g., ultraclean air systems for implant surgery. In elective surgery, the source of bacteria that cause infection is either the patient's normal flora (e.g., skin or bowel), i.e., endogenous, or the surgical staff or environment, i.e., exogenous. Surgical expertise and theater discipline are essential components in the fight against surgical sepsis.

During the past 30 years, antibiotic prophylaxis has proved of enormous efficacy in reducing the incidence of surgical wound infections, postoperative morbidity and mortality, the duration of the postoperative period, and the overall cost of surgical treatment. In this paper, the timing and route of administration of antibiotic prophylaxis as well as the dosage and duration, the indications for antibiotic prophylaxis, the importance of the alterations of the delayed hypersensitivity response, and the value of antibiotic prophylaxis for prevention of postoperative septic complications in anergic patients are analyzed. The possibility of combining antibiotic prophylaxis with immunoprophylaxis for high-risk patients is also analyzed.

Background: Oral therapy for patients with complicated intra-abdominal infections has been very limited because those patients are frequently ill and need surgery. In addition, at the time of diagnosis and initial treatment, the infection is often accompanied by ileus, gastrointestinal tract function is frequently unknown, and many patients cannot tolerate oral intake. The use of oral antimicrobials in this setting is a recent advance resulting from the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity. This is the first prospective blinded study of oral therapy to provide data on the characteristics of patients eligible for oral treatment and the consequences of such treatment.

Study design: In blinded fashion, patients with complicated intra-abdominal infections were randomized to either i.v. ciprofloxacin plus metronidazole or i.v. imipenem throughout their treatment course, or i.v. ciprofloxacin plus metronidazole and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ i.v./oral). Physicians could switch the patient to oral therapy between 3 and 8 days after the start of i.v. treatment.

Results: One hundred fifty-five of 330 (47%) patients were switched to active or placebo oral therapy. Patients who received i.v./oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment. Of 46 CIP/MTZ i.v./oral patients (active oral arm), treatment failure occurred in 2 patients (4%) compared with 41 patients (23%) who were not switched to oral agents. No patient or disease features, such as Acute Physiology and Chronic Health Evaluation II score, severity of illness at study entry, organ source of infection, or duration of treatment were identified as predictors of conversion to oral treatment.

Conclusions: In this first prospective examination of sequential i.v./oral therapy for complicated intra-abdominal infections, conversion to oral therapy with ciprofloxacin plus metronidazole appears as effective as continued i.v. therapy for patients able to tolerate oral feedings. Patients who can tolerate oral intake may be treated with appropriate oral antimicrobials and are not at any significant increased risk for failure.

Prosthetic devices are used extensively in surgical practice. This includes devices used on a temporary, intermittent, and long-term basis. In addition to problems with biocompatibility, the main health care issue concerning prostheses is the elevated risk of infection and the current inability to effectively prevent and treat such infections. An appreciation of microbial biofilm development has drawn attention to flaws in diagnosis and led to new methods to attack the problem. Future remedies will likely involve utilization of new biomaterial designs and application of either highly potent antimicrobials or agents used in combination that penetrate biofilms and eradicate the organisms.

The importance of postoperative infections depends on the frequency with which infection occurs as well as on the additional cost per patient with infection. For example, in our hospital the additional cost per patient with infection after hernia repair was $600, compared with $2,106 per patient with infection after colonic surgery. However, the total excess cost per year was similar for hernia surgery ($44,800) and colon surgery ($48,440). The reason is that hernia surgery is much more common than colon surgery. It is a general principle of clinical audit that the importance of problems should be defined by their frequency as well as their individual severity. A third important consideration is the likelihood that the problem can be corrected. Undue attention has been given to the health resource costs of postoperative infection at the expense of information about the intangible costs to the patient (these are nonfinancial costs such as pain and disability). Health resource costs are very dependent on medical practice variation, and comparative studies between countries reveal marked differences in the way that apparently similar infections are managed. Moreover, comprehensive audit of infection-control management often reveals wasteful practice, e.g, antibiotic treatment of patients who do not in fact have infection. Audit of postoperative infection should focus on eliminating wasteful practice (e.g., prophylactic antibiotics continuing > 24 hrs after surgery) as well as on reducing postoperative infection rates.

Hypovolemic shock is a common disease treated in pediatric ICUs and emergency departments worldwide. A wide variety of etiologic factors may cause this disease, with the common net result of decreased intravascular volume leading to decreased venous return to the heart and decreased stroke volume. Inadequate perfusion results in impairment of delivery of nutrients and oxygen to vital end organs. With the advent of pediatric critical care and pediatric emergency medicine as specialties, deaths from hypovolemic shock have become increasingly rare in the United States. The physical signs of hypovolemic shock in children must be quickly recognized, and aggressive volume resuscitation must be administered before irreversible end-organ dysfunction occurs. This is best accomplished by large peripheral or central intravenous access, with intraosseous access an alternative option in the pediatric patient. The amount as well as the type of volume administered must be tailored for each individual patient, taking into account the amount of intravascular depletion and the disease state in which the shock has occurred. It is not uncommon for children to require large amounts of fluid for resuscitation, and close attention must be paid to children with fluid-refractory shock, who may require catecholamine and/or exogenous steroid support in combination with aggressive fluid resuscitation.