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Query: UMLS:C0036690 (sepsis)
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Continuous renal replacement therapies (CRRT) are now being used by nephrologists, intensivists, and anesthesiologists. The various CRRT modalities differ in the kind of vascular access, the application of diffusive or convective clearances (or a combination of both), and in the location where the replacement fluid enters the circuit. CRRTs have certainly made the management of critically ill patients with acute renal failure (ARF) combined with cardiovascular instability, severe fluid overload, hypercatabolism, cerebral edema, adult respiratory distress syndrome, lactic acidosis, sepsis or other inflammatory syndromes, crush syndrome, congestive heart failure, and cardiopulmonary bypass easier. Continuous therapies incorporate several advantages including improved hemodynamic stability, optimal fluid balance, gradual urea removal, elimination of septic mediators, and the possibility of unlimited parenteral nutrition. Major difficulties and unsolved problems of CRRT are the ongoing necessity of continuous anticoagulation, considerable loss of amino acids, vitamins, trace elements, potassium, phosphate, and some drugs, as well as immobilization of the patient. The advantages of CRRT should theoretically translate into improved outcomes of critically ill ARF patients, but the superiority of continuous modalities in terms of outcome is still controversial, despite encouraging results in some clinical trials. Currently used CRRT with sophisticated treatment devices has become more expensive than hemodialysis, but the cost cannot be used as an argument against the continuous treatment modalities.
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PMID:Slow continuous renal replacement therapies: an update. 1102 12

Fluid imbalance can arise due to hypovolemia, normovolemia with maldistribution of fluid, and hypervolemia. Trauma is among the most frequent causes of hypovolemia, with its often profuse attendant blood loss. Another common cause is dehydration, which primarily entails loss of plasma rather than whole blood. The consequences of hypovolemia include reduction in circulating blood volume, lower venous return and, in profound cases, arterial hypotension. Myocardial failure may result from increased myocardial oxygen demand in conjunction with reduced tissue perfusion. Finally, anaerobic metabolism due to reduced perfusion may produce acidosis and, together with myocardial dysfunction, precipitate multi-organ failure. The splanchnic organs are particularly susceptible to the deleterious effects of hypotension and hypovolemic shock, and these effects, depending upon their duration and severity, may be irreversible despite restoration of normovolemia by fluid administration. Patient monitoring in the intensive care unit typically relies upon central venous pressure devices, whereas the primary focus in the operating theater is blood volume deficit estimated from suction devices. However, estimates of intraoperative blood loss can be inaccurate, potentially leading to inappropriate fluid management. Normovolemia with maldistribution of fluid can be encountered in shock-specific microcirculatory disorders secondary to hypovolemia, as well as pain and stress. Consequent vasoconstriction and reduced tissue driving pressure, as well as leukocyte and platelet adhesion, and liberation of humoral and cellular mediators, may impair or abolish blood flow in certain areas. The localized perfusion deficit may contribute to multi-organ failure. Choice of resuscitation fluid may be important in this context, since some evidence suggests that at least certain colloids might be helpful in diminishing post-ischemic microvascular leukocyte adherence. Excessive volume administration may lead to fluid overload and associated impairment of pulmonary function. However, entry of fluid into the lungs may also be facilitated by increased vascular permeability in certain pathologic conditions, especially sepsis and endotoxemia, even in the absence of substantially rising hydrostatic pressure. Another condition associated with elevated vascular permeability is systemic capillary leak syndrome. The chief goal of fluid management, based upon current understanding of the pathophysiology of fluid imbalance, should be to ensure adequate oxygen delivery by optimizing blood oxygenation, perfusion pressure, and circulating volume.
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PMID:Pathophysiology of fluid imbalance. 1125 92

Because continuous renal replacement therapy (CRRT) may enhance inflammatory mediator removal, this review assesses its impact on multiple organ failure (MOF). Regarding MOF with acute renal failure (ARF), the overall mortality of 2313 CRRT patients (43 studies) was 62.8% compared with 59.1% (p = 0.046) in 961 intermittent hemodialysis (IHD) patients (12 other studies). Of 13 CRRT studies with an IHD comparison group, 3 showed that the groups had a similar risk, but IHD mortality was higher; 1 noted that CRRT had lower mortality (risk not stated); and 4 showed similar mortality and greater CRRT risk. Aggregate mortality was IHD 69.5% and CRRT 63.9% (p = 0.02). Of the six studies with matched groups (age and APACHE II scores), IHD mortality was higher (70.9% vs. 60.1%, p = 0.01). CRRT pulmonary gas exchange, hemodynamic instability, azotemia control, fluid overload, and nutritional support were better. Regarding MOF without ARF, of 14 CRRT studies (14.5 patients per study), only 4 had comparison groups. Patient conditions were as follows: acute respiratory distress syndrome, six studies; sepsis, three studies; septic shock, two studies; pancreatitis, one study; critically ill patients, one study; and cardiac surgery with respiratory failure, one study. Of the three studies with a control group, the mortality was the same. There was minimal evidence that CRRT improved pulmonary gas exchange or hemodynamic instability. For MOF patients with ARF, there is compelling evidence that CRRT provides better survival than IHD and more improvement in pulmonary gas exchange, hemodynamic instability, azotemia control, fluid overload, and nutritional support. In patients with MOF and no renal failure, there is little evidence that CRRT enhances survival, oxygenation, or perfusion. Controlled trials demonstrating a CRRT benefit are necessary before CRRT can be recommended for MOF without ARF.
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PMID:Clinical impact of continuous renal replacement therapy on multiple organ failure. 1139 37

During the final prenatal period of fetal lung development in humans, important maturational processes occur, including the production of surfactant necessary to decrease surface tension at the air-liquid interface of the alveoli. During early gestation, the glucocorticoid receptor is expressed in the fetal lung, and glucocorticoids stimulate the production of surfactant-associated proteins and increase phospholipid synthesis by enhancing the activity of phosphatidylcholine. Other glucocorticoid-induced effects may include stimulation of cell maturation and differentiation, inhibition of DNA synthesis, changes in interstitial tissue components, stimulation of antioxidant enzymes, and regulation of pulmonary fluid metabolism. Recently, it was suggested that glucocorticoids are also important in postnatal pulmonary development, and may be related to the development of neonatal lung disease in preterm infants. Surfactant deficiency that can be prevented by antenatal corticosteroid treatment causes infant respiratory distress syndrome and requires mechanical ventilation. Ventilation by itself or in combination with high levels of oxygen, fluid overload, pulmonary infections, sepsis, and air leak syndrome causes an acute pulmonary inflammatory reaction that may result in chronic lung disease or bronchopulmonary dysplasia. Glucocorticoids are effective in the treatment of chronic lung disease of prematurity and regulate the inflammatory response by the interaction with transcription factors such as nuclear factor kappaB and activated protein 1. Indeed, inflammatory cells and the levels of chemokines and cytokines in bronchoalveolar fluid decrease after dexamethasone treatment. However, treatment of fetuses and preterm infants with repeated and/or high doses of corticosteroids may have considerable long-term side effects on somatic, brain, and lung growth. The difficult balance between short-term gain and the possible long-term side effects of glucocorticoids in preterms remains a difficult issue.
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PMID:Glucocorticoids and lung development in the fetus and preterm infant. 1141 80

This review evaluates the various causes and management of acute renal failure (ARF) in children. ARF is defined as an abrupt decline in the renal regulation of water, electrolytes and acid-base balance, and continues to be an important factor contributing to the morbidity and mortality of critically ill infants and children. The common causes of ARF in children include acute tubular necrosis secondary to various causes (including congestive heart failure and sepsis), haemolytic uremic syndrome, and glomerulonephritis and urinary tract obstruction. Ischaemia, toxins (including drugs) as well as primary parenchymal disease, have to be considered and ARF can also be a complication of systemic disease. The basic principles of management are avoidance of life-threatening complications, maintenance of fluid and electrolyte balance, and nutritional support. Only a few patients require specific management of the underlying disorder, although it is important to diagnose these conditions. Knowledge about the use of drugs for the prevention of ARF is scarce. Mannitol, low-dose dopamine, calcium channel antagonists, atrial natriuretic peptide and albumin have been evaluated and, where possible, meta-analyses are cited. Mannitol treatment appears to be warranted prophylactically after paediatric renal transplantation. Albumin infusion can reverse prerenal ARF in children with nephritic syndrome. For treatment of the complications of hyperkalaemia and volume overload, salbutamol, insulin and glucose infusion and diuretics such as furosemide and sodium bicarbonate, are discussed. All of the major dialysis modalities (peritoneal dialysis, haemodialysis and continuous haemofiltration) can be used to provide equivalent solute clearance and ultrafiltration. The indication for, and the choice of the modality depend on the patient requirements and on local resources, and should involve the care of a paediatric nephrologist. Peritoneal dialysis requires minimal equipment and infrastructure, is easy to perform and remains the favoured modality of renal replacement therapy in children. However, continuous haemofiltration is an excellent alternative to peritoneal dialysis in patients with ARF and severe fluid overload. Dialysis remains the most important tool to bridge the time needed for recovery of renal function. There is increasing evidence that more intense use of dialysis may improve the overall prognosis.
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PMID:Acute renal failure in children: aetiology and management. 1173 64

Continuous arteriovenous haemofiltration (CAVH) is the first example of continuous renal replacement therapy (CRRT). CAVH was first applied for the treatment of diuretic unresponsive fluid overload. Subsequently, CRRT has undergone a remarkable growth, and it is now performed with pump technology (CVVH) and via double-lumen central venous catheters. In many intensive care units, especially in Australia and in Europe, CRRT has become the dominant, if not exclusive, form of artificial renal support. Continuous haemofiltration is now used beyond the original indications of blood purification, for the treatment of certain drug intoxications, for severe cardiac failure, for volume control during, after cardiopulmonary bypass, and to decrease the toxicity of chemotherapy. Furthermore, there is strong ongoing research into its role or that of derived techniques as possible adjuvant therapies during severe sepsis. Despite its large use, the current state of CRRT is surrounded by some controversies, and an effort should be made to give a dispassionate distillation of the literature for a final common definition of what is based on opinions and what carries sufficient evidence.
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PMID:Continuous renal replacement therapy: opinions and evidence. 1238 23

The clinical course of HIV seropositive renal allograft recipients is ill defined. Thus, a retrospective analysis of mortality, morbidity and graft survival was performed in two groups of HIV-positive patients. Group 1 (nine patients), seropositive for an indefinite period of time prior to transplantation (eight i.v. drug abusers, one homosexual), all lost their grafts after a mean period of 23 +/- 11 months from chronic rejection (six), complicated by focal glomerular sclerosis and nephrotic syndrome in three cases, sepsis (two) and death with a functioning graft (one). Four patients died, two from sepsis, one from Kaposi's sarcoma and one from fluid overload. Of the remaining five patients, all on hemodialysis, one had AIDS and four were asymptomatic after a mean period of 44 months following graft failure. Prolonged hospitalizations for both infections and acute rejection were common. Group 2 (six patients) seroconverted in the perioperative period, and two had functioning allografts at 78 and 100 months post-transplant. Causes of allograft loss, patient death and infection-related complications were similar to those of group 1, but acute rejection was rare. In conclusion, HIV infection in renal allograft recipients was associated with poor allograft survival due mainly to rejection, mostly chronic, often complicated by glomerular sclerosis and nephrotic syndrome. Infectious complications requiring hospitalization were also increased.
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PMID:The course of HIV disease in renal allograft recipients. 1462 55

Fluid overload may occur in patients with myocardial dysfunction and different clinical problems. Myocoardial dysfunction may be a consequence of heart dilatation with reduced contractility, ventricular stiffness with diastolic dysfunction or the consequence of myocardial injury or circulating myocardial depressant factors as seen in sepsis. In all cases, cardiac support can be achieved by the optimization of fluid balance, the reduction in organ edema and the restoration of desirable levels of pre- and afterload. Several reports have shown that myocardial elastance can improve after hemofiltration with restoration of adequate fluid balance. In such conditions, continuous extracorporeal therapy may result in remarkable cardiovascular stability with maintenance of hemodynamic parameters, including mean arterial pressure, heart rate and systemic vascular resistance. Such stability, which is achieved through the slow continuous ultrafiltration and continuous refilling of the intravascular volume from the interstitium, enables the stability of the circulating blood volume and the preservation of organ perfusion. This is also crucial for renal recovery during acute renal failure.
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PMID:Ultrafiltration in patients with hypervolemia and congestive heart failure. 1473 24

Classical familial amyloid polyneuropathy may have a course with progressive renal impairment. We studied 62 patients (24 males, 38 females) with FAP, transthyretin variant V30M, and end-stage renal disease (ESRD) treated with hemodialysis, all referred to a single center over a period of 11 years. Clinical course, morbidity and survival after dialysis were analyzed. Patient's mean age at first dialysis was 51.5 +/- 10.7 years, and mean duration of neuropathy was 10.2 +/- 3.8 years. The most frequent form of presentation of FAP nephropathy was nephrotic proteinuria with renal dysfunction. In the year prior to dialysis, renal function declined rapidly, and fluid overload was the main indication to initiate treatment. The presence of decubitus ulcers, significant disability, venous catheter for definitive vascular access for long-term treatment, and permanent bladder catheter, were related to death during the first year of dialysis. The mean duration of renal replacement therapy was 21 months, with a 54.5% one year, and 38.4% two year treatment survival. However, when the duration of neurological symptoms at first dialysis exceeded 10 years, survival was significantly lower. Infections, (41% were decubitus ulcers with sepsis) were the cause of early, as well as late mortality. Early creation of vascular access for hemodialysis, surveillance of skin wounds, and intervention on neurogenic bladder are essential to improve the prognosis of ESRD in FAP.
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PMID:End-stage renal disease and dialysis in hereditary amyloidosis TTR V30M: presentation, survival and prognostic factors. 1518 96

A 5-day-old newborn presented with neonatal enteroviral infection. The patient's hospital course was complicated by acute liver dysfunction, renal insufficiency, fluid overload, respiratory failure, hypertension, catheter related thrombosis, Klebsiella pneumoniae sepsis, intracerebral and intraventricular hemorrhage, and disseminated intravascular coagulation (DIC). Administration of fresh frozen plasma (FFP) and cryoprecipitate failed to control the patient's hemostasis and led to significant fluid overload. Recombinant activated factor VII (rFVIIa, Novoseven NovoNordisk, Bagsvaerd, Denmark) was given to the neonate as a bolus (rFVIIa at 60-80 microg/kg body weight), followed by a continuous infusion (2.5-16 microg/kg/hr). Recombinant activated factor VII controlled hemostasis, until the patient's liver function recovered. The patient's blood product requirement significantly decreased and his fluid overload resolved. Administration of rFVIIa appears to have stabilized the coagulation process. The patient appears to have fully recovered from the infection's complications.
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PMID:Management of coagulopathy with recombinant factor VIIa in a neonate with echovirus type 7. 1523 86


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