Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Pulse High-Volume Hemofiltration in Management of Critically Ill Patients With Severe Sepsis or Septic Shock
Objectives
This chapter will:
- 1.
Assess the safety, feasibility, and technical considerations with use of pulse high-volume hemofiltration as an adjuvant therapy for critically ill patients with sepsis or septic shock.
- 2.
Review the rationale for the use of pulse high-volume hemofiltration in this clinical setting.
- 3.
Evaluate the current clinical and experimental evidence supporting the use of pulse high-volume hemofiltration as an adjuvant therapy for critically ill patients with severe sepsis or septic shock.
- 4.
Highlight possible future lines of investigation for applications of pulse high-volume hemofiltration.
Sepsis is the leading cause of morbidity and mortality and the main reason to start renal replacement therapy among critically ill patients worldwide. Despite current advances in the understanding of the pathophysiology of this complex syndrome, mortality rates associated with sepsis remain between 30% and 45%, reaching up to 60% in septic shock, which seems unacceptably high.
The sepsis syndrome is associated with an overwhelming systemic overflow of proinflammatory and antiinflammatory mediators, leading to generalized endothelial damage, multiple organ failure, and altered cellular immunologic responsiveness, inducing in turn a state of immunoparalysis or monocyte hyporesponsiveness.
The last several years have seen a growing interest in the role of blood purification techniques with high ultrafiltration volumes in an attempt to enhance unselective clearance of water-soluble proinflammatory and antiinflammatory cytokines produced during septic states, theoretically restoring humoral homeostasis and avoiding excessive inflammation and “antiinflammation.” In a seminal study by Ronco et al. that included 425 patients, continuous venovenous hemofiltration (CVVH) was used at three different ultrafiltration rates: 20 mL/kg per hour (group 1), 35 mL/kg per hour (group 2), and 45 mL/kg per hour (group 3). Survival rates were significantly lower in group 1 than in groups 2 and 3. The survival rates among patients from groups 2 and 3 were not significantly different from one another except for the subgroup of septic patients in which the survival increased with higher ultrafiltration volumes (18% in group 2 vs. 47% in group 3), suggesting that this group may benefit from higher doses of blood replacement.
High-volume hemofiltration (HVHF) is a variant of CVVH that uses ultrafiltration rates higher than 40 mL/kg/hr. In sepsis and multiple organ failure syndrome (MODS), HVHF is applied with the aim of nonselective removal of pro- and antiinflammatory mediators by enhancing convective clearance and adsorption of these molecules by the filtering membrane.
Multiple in vitro studies have demonstrated the ability of HVHF to remove cytokines involved in sepsis. Animal studies have shown beneficial hemodynamic effects and improved survival with the use of HVHF in endotoxemic models.
Available observational studies in humans have shown trends toward improved observed versus predicted mortality in septic patients treated with HVHF. Unfortunately, these studies exhibit considerable variability in terms of population studied, inclusion criteria, hemofiltration schedules, and clinical definition of response to therapy, making it difficult to set up any clinical guideline to assess this controversial issue.
A recent randomized controlled trial comparing standard (30 mL/kg/hr) versus high-volume (70 mL/kg/hr) 96 hours of continuous hemofiltration in critically ill patients with septic shock and acute kidney injury (AKI) failed to demonstrate the impact of CHVHF in 28-day survival. Anyway, the trial was underpowered to demonstrate any benefit of CHVHF because of inability to reach the sample size. Authors hypothesize that the lack of benefit may be related to the fact that CHVHF was associated with a significant grater clearance of antibiotics and electrolites as compared with standard volume hemofiltration.
In this sense, recently some authors have expressed concern about safety of continuous forms of HVHF, particularly considering its effects on removal of electrolytes and divalent ions, water-soluble vitamins and trace elements, heat loss, and enhanced clearance of drugs, particularly antibiotics. This concept has been called dialytrauma, and it must be considered as a possible problem when starting CHVHF.
Beside concerns about safety and clinical utility, performing CHVHF may be associated with logistic problems because of the need for high blood flows, tight ultrafiltration control, and large amounts of sterile fluids, which are expensive. The technical requirements of HVHF have generated some concern about its feasibility and cost for use as a continuous-treatment modality.
Definition and Rationale
Recently, Ronco et al. proposed pulse high-volume hemofiltration (PHVHF) as a modality that reduces practical and technical difficulties associated with CHVHF, potentially attenuating the effects of the so-called “dialytrauma.”
PHVHF consists of the application of HVHF for short periods of time, providing intensive plasma water exchange, followed by conventional CVVH. It consists of a daily schedule of HVHF (at 85 mL/kg/hr) for 6 to 8 hours, followed or preceded by CVVH (at 35 mL/kg/hr) for the remaining time, leading to a cumulative dose of approximately 48 mL/kg/hr ( Fig. 172.1 ). The schedule can be modified according to the patient's response and needs, and as required by organizational considerations, in an attempt to maximize cost effectiveness and practical application of HVHF.
Previous studies by Honoré and Piccinni et al. have evaluated the clinical outcomes for patients receiving pulses of high ultrafiltration volumes followed by conventional CVVH. In a retrospective study by Piccinni et al., 80 oliguric septic patients underwent renal replacement therapy. Forty patients received conventional CVVH with ultrafiltration volume 20 mL/kg per hour only for conventional indications (control group), and the other 40 patients were selected to receive, within 12 hours of admission, 6 hours of HVHF (45 mL/kg/hr), followed by conventional CVVH (intervention group). The intervention group showed a significant decrease in norepinephrine dose and improvement in gas exchange, cardiac index, mean arterial pressure, systemic vascular resistance, and urine output compared with the control subjects. Although mortality rates predicted by Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) severity scores were similar in both groups (41 ± 12% in intervention group patients vs. 40 ± 10% in control subjects), the 28-day survival rate was significantly better in the intervention group (55%) than in the control group (11%).
In a prospective trial by Honoré et al., 20 patients with intractable cardiocirculatory failure complicating septic shock underwent 4 hours of HVHF with removal of 35 L of ultrafiltrate, followed by conventional CVVH exchanging 24 L per day for at least 4 days. Among the 11 patients considered responders (evidenced by a greater than 50% increase in cardiac index, greater than 25% increase in mixed venous saturation, increase in pH to above 7.3, and a greater than 50% reduction in epinephrine dose), the 28-day mortality rate was significantly lower in the responders group. After the 35-L exchange volume was indexed to individual patient body weight, ultrafiltrate dose was found to be significantly higher in responders (0.53 ± 0.07 L/kg) than in nonresponders (0.43 ± 0.07 L/kg; p < .003).
The pathogenic role of apoptosis in organ injury during sepsis is recognized increasingly. Apoptosis is accelerated in monocytes during sepsis, a fact that may contribute to “monocyte hyporesponsiveness” and impaired host defense capacity. D'Intini et al. recently studied the effect of PHVHF on monocyte apoptotic activity: Septic plasma-induced pronounced apoptotic effects on U937 human monocytic cells compared with those observed in controls. PHVHF but not CVVH significantly reduced the apoptotic plasma activity by the first hour of therapy; this effect was maintained at 5 hours of treatment and at 5 hours after the end of the pulse therapy. These results highlight potential biologic effects of PHVHF on sepsis beyond hemodynamic improvement.
The rationale for use of PHVHF scheduling rests on practical and biologic considerations. Practical advantages are related to easier management of large fluid exchanges for a short period of time as compared with continuous handling of large volume exchanges of expensive substitution fluids in HVHF. The biologic rationale relies on the fact that pulse HVHF can remove a large amount of mediators, and the continuity of therapy with conventional CVVH may curtail the peak of proinflammatory and antiinflammatory mediators such as IL-10 avoiding potential adverse effects of HVHF on the internal milieu and pharmacokinetics of antibiotics. In fact, a recent study by Chu et al. demonstrated that a single session of 6 hours PHVHF (85 mL/kg/hr) was associated with significantly lower levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-10 (IL-10) as compared with conventional CVVH (35 mL/kg/hr) in a cohort of patients with multiple organ dysfunction syndrome in the setting of acute severe pancreatitis.
According to the peak concentration hypothesis, the amputation of the proinflammatory peak will reduce endothelial damage and vasoparalysis, whereas the amputation of the antiinflammatory peak secreted in response to the proinflammatory mediators will be important in maintaining a certain cell responsiveness to endotoxemia and bacteremia, with preservation of the immunologic response. The continuous nature of the technique and the double-pool kinetics for different mediators allow long-term maintenance of lowered levels.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here