A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF.

This review will cover septic shock as a manifestation of severe sepsis. The reader is referred to other articles, which review the myriad multisystem dysfunctions associated with severe sepsis (1– 4), and is reminded that as in all patients with sepsis early initiation of appropriate antibiotics and adequate source control are key components of septic shock treatment. Ascertaining the incidence of septic shock is limited by the variability in definitions used in epidemiologic studies, the analysis of septic shock as a subset of patients with severe sepsis, and shortcomings of methods used to calculate the incidence of severe sepsis. In five recent large clinical trials that enrolled a total of 5,461 patients with severe sepsis (criteria evidence of infection, systemic inflammatory response syndrome, and at least one organ dysfunction/hypoperfusion), the incidence of septic shock ranged from 52% to 71% of patients with severe sepsis, with a mean of 58% (5–9). A recent study used International Classification of Diseases (ICD)-9 hospital diagnostic codes for infection and acute organ dysfunction to estimate 751,000 cases of severe sepsis per annum in the United States (10). Taking the incidence of septic shock in severe sepsis from the five studies above, septic shock would, therefore, be predicted to occur annually in 435,580 patients in the United States. The mortality of septic shock can be estimated more reliably. Table 1 shows a compilation of septic shock mortalities drawn from the placebo arms of clinical trials (8, 9, 11–22). Figure 1 shows improvement in septic shock mortality over time (23). Historical Perspective The word sepsis is derived from the Greek language (24). Pepsis was good, embodying the natural processes of maturation and fermentation. Sepsis, however, was bad and synonymous with putrefaction as characterized by bad smell. It was thousands of years later before Pasteur conclusively linked putrefaction to a bacterial cause. The word shock has its derivation from the French root “choquer,” meaning “to collide with.” Based on our current understanding of the pathophysiology of septic shock, the collision of the body’s defenses with the invading organism, this seems to be particularly appropriate terminology.

http://medical-mastermind-community.com/uploads/Vasopressors-in-Sepsis.pdf

Cardiovascular management of septic shock.

Background. Mortality rates of critically ill patients with acute renal failure (ARF) requiring renal replacement therapy (RRT) are high. Intermittent and continuous RRT are available for these patients on the intensive care units (ICUs). It is unknown which technique is superior with respect to patient outcome. Methods. We randomized 125 patients to treatment with either continuous venovenous haemodiafiltration (CVVHDF) or intermittent haemodialysis (IHD) from a total of 191 patients with ARF in a tertiary-care university hospital ICU. The primary end-point was ICU and in-hospital mortality, while recovery of renal function and hospital length of stay were secondary end-points. Results. During 30 months, no patient escaped randomization for medical reasons. Sixty-six patients were not randomized for non-medical reasons. Of the 125 randomized patients, 70 were treated with CVVHDF and 55 with IHD. The two groups were comparable at the start of RRT with respect to age (62±15 vs 62±15 years, CVVHDF vs IHD), gender (66 vs 73% male sex), number of failed organ systems (2.4±1.5 vs 2.5±1.6), Simplified Acute Physiology Scores (57±17 vs 58±23), septicaemia (43 vs 51%), shock (59 vs 58%) or previous surgery (53 vs 45%). Mortality rates in the hospital (47 vs 51%, CVVHDF vs IHD, P ¼ 0.72) or in the ICU (34 vs 38%, P ¼ 0.71) were independent of the technique of RRT applied. Hospital length of stay in the survivors was comparable in patients on CVVHDF [median (range) 20 (6–71) days, n ¼ 36] and in those on IHD [30 (2–89) days, n ¼ 27, P ¼ 0.25]. The duration of RRT required was the same in both groups. Conclusion. The present investigation provides no evidence for a survival benefit of continuous vs intermittent RRT in ICU patients with ARF.

/pdf/comparison-of-continuous-and-intermittent-renal-replacement-2pj1f4lyo2.pdf

Comparison of continuous and intermittent renal replacement therapy for acute renal failure

https://www.ajkd.org/article/S0272-6386(04)01256-9/pdf

Pathogenesis and Treatment of Kidney Disease and Hypertension A Randomized Controlled Trial Comparing Intermittent With Continuous Dialysis in Patients With ARF

Objective To study the effect of early and continuous venovenous hemofiltration (CVVH) on the plasma concentrations of several humoral mediators of inflammation and subsequent organ dysfunction in septic patients. Design Randomized, controlled trial. Setting Intensive care unit of a tertiary hospital. Patients Twenty-four patients with early septic shock or septic organ dysfunction. Interventions Random allocation to receive 48 hrs of isovolemic CVVH at 2 L/hr of fluid exchange or no hemofiltration. Measurements and main results We measured the plasma concentrations of complement fractions C3a and C5a, interleukins 6, 8, and 10, and tumor necrosis factor alpha at baseline and 2, 24, 26, 48, and 72 hrs. A multiple organ dysfunction score (MODS) was calculated daily for each patient until death or discharge from the intensive care unit. The concentrations of most mediators decreased between baseline and 72 hrs. Some significant falls in concentration could be identified between specific time points, but CVVH was not associated with an overall reduction in any plasma cytokine concentrations. There was also no difference between the mean cumulative MODS for control survivors (43.3 +/- 19.7) and CVVH survivors (33.2 +/- 19.0; p = .30), and no difference between the average MODS calculated for all controls (4.1 +/- 1.9) and all CVVH subjects (3.3 +/- 1.7; p = .26). CVVH did not improve oxygenation, lower the platelet count, or reduce the duration of vasopressor support and mechanical ventilation. Conclusions Early use of CVVH at 2 L/hr did not reduce the circulating concentrations of several cytokines and anaphylatoxins associated with septic shock, or the organ dysfunction that followed severe sepsis. CVVH using current technology cannot be recommended as an adjunct to the treatment of septic shock unless severe acute renal failure is present.

A phase II randomized, controlled trial of continuous hemofiltration in sepsis.

A potential application of the continuous renal replacement therapies is the extracorporeal removal of inflammatory mediators in septic patients Cytokine elimination with continuous renal replacement therapies has been demonstrated in several clinical studies, but so far without important effects on their serum concentrations Improved knowledge of the cytokine removal mechanisms could lead to the development of more efficient treatment strategies In the present study, 15 patients with septic shock and acute renal failure were observed during the first 24 h of treatment with continuous venovenous hemofiltration (CVVH) with an AN69 membrane After 12 h, the hemofilter was replaced and the blood flow rate (QB) was switched from 100 ml/min to 200 ml/min or vice versa Pre- and postfilter plasma and ultrafiltrate concentrations of selected inflammatory and anti-inflammatory cytokines were measured at several time points allowing the calculation of a mass balance Cytokine removal was highest 1 h after the start of CVVH and after the change of the membrane (ranging from 25 to 43% of the prefilter amount), corresponding with a significant fall in the serum concentration of all cytokines The inhibitors of inflammation were removed to the same extent as the inflammatory cytokines Adsorption to the AN69 membrane appeared to be the main clearance mechanism, being most pronounced immediately after installation of a new membrane and decreasing steadily thereafter, indicating rapid saturation of the membrane A QB of 200 ml/min was associated with a 75% increase of the ultrafiltration rate and a significantly higher convective elimination and membrane adsorption than at a QB of 100 ml/min The results indicate that optimal cytokine removal with CVVH with an AN69 membrane could be achieved with a combination of a high QB/ultrafiltration rate and frequent membrane changes

http://www.nimbot.com/Med/Articles/Journal%20Clubs/2007-02/Cytokine%20removal%20during%20continuous%20hemofiltrationin%20septic%20patients.pdf

Cytokine Removal during Continuous Hemofiltration in Septic Patients

Aim: Evaluation of renal function and relation to risk factors for renal failure in very old patients admitted to an acute geriatric ward. Methods: Retrospective chart review ofpatients aged 80 years and over, admitted to the acute geriatric ward from August 1998 till August 1999. Recorded data were: age,gender, previous medical history, primary diagnosis, medicationuse, weight, serum creatinine, BUN, sodium, potassium,cholesterol, urine and ultrasound of the kidney. The creatinine clearance was estimated by the Cockcroft-Gault formula, the glomerular filtration rate by the MDRD equation. Results: 220 (60males/160 females) patients were included. The mean serum creatinine on admisssion and discharge was 1.17 ± 0.45 mg/dL and1.11 ± 0.48 mg/dL respectively. The mean estimated creatinine clearance in the very old was 38.11 ± 12.04 mL/min on admissionand 39.00 ± 11.01 mL/min on discharge. Renal failure arbitrarily defined as an estimated creatinine clearance on admission of less than 30 mL/min was found in 26.4% of the patients. Only a significant correlation between failure to thrive and renal failure was found (p < 0.0001). The correlation coefficient between the Cockcroft-Gault and the MDRD formula was r = 0.66 (p < 0.0001);between the Cockcroft-Gault and the reciprocal serum creatinine wasr = 0.60 (p < 0.0001) and between the MDRD and the reciprocal serum creatinine was r = 0.87 (p < 0.0001). Conclusion: The weak correlation between the Cockcroft-Gault and other estimations ofGFR in the acutely ill elderly, confirms the need to have areliable estimation of glomerular filtration rate in the elderly.Renal failure defined as a Cockgroft-Gault <30 mL/min is foundin 26.4% of the oldest-old admitted to an acute geriatric department. The elderly with renal failure is more often admitted for failure to thrive. No great differences were observed between renal function on admission and discharge.

Renal function in the oldest-old on an acute geriatric ward

The prognosis of acute renal failure (ARF), as judged by mortality rates, has not improved over the last few decades. This is remarkable in view of the improvement in dialysis techniques, better blood access, the use of hyperalimentation and more efficient antibiotics. This lack of continued improvement has been attributed to two major factors: An increase in the age of patients who develop ARF, and an increase in the proportion of patients who present with other significant illnesses, complicated by ARF.

Acute renal failure in the elderly.

In this article the different dialysis strategies in the management of acute renal failure (ARF) in the elderly are discussed. Although peritoneal dialysis (PD) offers some theoretical advantages, there are several medical and technical reasons why it is currently less frequently used. The choice between intermittent hemodialysis (HD) and continuous renal replacement therapy (CRRT) is determined by a number of considerations, the most important ones being hemodynamic stability, the need for hyperalimentation and/or ultrafiltration, and the local experience with one or both techniques. Some recent studies with CRRT in elderly ARF patients describe favorable results. Slow extended daily dialysis (SLEDD) modalities may be particularly indicated in elderly, critically ill ARF patients because these techniques combine the advantages of both CRRT and HD. Finally, the importance of the biocompatibility of dialysis membranes is discussed. Although there are a number of theoretical arguments to use biocompatible membranes, this opinion is not always supported by the results of recent comparative studies. It is the opinion of the authors that all dialysis strategies should be mastered and utilized for appropriate indications in elderly ARF patients.

The dialytic management of acute renal failure in the elderly.

Patients with acute renal failure [ARF] increasingly require management in an Intensive Care Unit, due to the fact that ARF occurs as a complication of a medical or surgical catastrophe, or as part of the multi-organ failure [MOF] syndrome. The presence of more than one organ failure adversely affects the overall prognosis, and creates additional management problems, that should be taken into account by the treating nephrologist.

Norbert Lameire

Papers

Cytokine Removal during Continuous Hemofiltration in Septic Patients

Renal function in the oldest-old on an acute geriatric ward

Acute renal failure in the elderly.

The dialytic management of acute renal failure in the elderly.

Principles of peritoneal dialysis and its application in acute renal failure