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In Vivo Antibiotic Removal During Coupled Plasma Filtration Adsorption: A Retrospective Study

Page, Mathieu*; Cohen, Sabine; Ber, Charles-Eric*; Allaouchiche, Bernard*; Kellum, John A.; Rimmelé, Thomas*

doi: 10.1097/MAT.0000000000000009
Renal
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Coupled plasma filtration adsorption (CPFA) is a blood purification therapy aimed at modulating the host inflammatory response involved in sepsis pathogenesis. One potential drawback of this technique is the unexpected elimination of antibiotics. The aim of this study was to assess the elimination of several antibiotics with CPFA. We performed a retrospective analysis of the serum and ultrafiltrate concentrations of different antibiotics routinely measured during CPFA sessions in five patients experiencing septic shock. The adsorbent extraction ratio (AER) for piperacillin and vancomycin 2 h into the CPFA session were high: 95.4 ± 6.9% and 99.6 ± 0.9%, respectively. These AER decreased significantly by 8 h (at 8 h: 6.3 ± 51.8% and −30.2 ± 25.6%, respectively), suggesting saturation of the resin cartridge. Conversely, the tazobactam AER was low (7.2 ± 15% after 2 h of CPFA). No significant changes in the mean serum concentrations of piperacillin, tazobactam, and vancomycin were observed. Thus, as opposed to tazobactam, we report high adsorption of piperacillin and vancomycin on the CPFA resin but with no reduction in serum concentrations.

From the *Department of Anesthesiology and Critical Care Medicine, Pavilion P, Edouard Herriot Hospital, Hospices Civils de Lyon, Claude Bernard University Lyon 1, Lyon, France; Laboratory of Toxicology and Biochemistry, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Claude Bernard University Lyon 1, Pierre-Bénite, France; and The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Submitted for consideration April 2013; accepted for publication in revised form September 2013.

Disclosure: T.R. received consulting fees from Bellco, Mirandola, Italy. The remaining authors have no conflicts of interest to report.

Reprint Requests: Mathieu Page, Department of Anesthesiology and Intensive Care Medicine, Pavilion P, Edouard Herriot Hospital, 5 place d’Arsonval, 69437 Lyon Cedex, 03 France. Email: page.mat@gmail.com.

Severe sepsis and septic shock remain major causes of mortality in the intensive care unit, with mortality rates ranging from 30% to 60%.1 A variety of blood purification techniques have been proposed to remove soluble pro- and anti-inflammatory mediators or endotoxins from the blood compartment during sepsis.2–4 The excessive release of inflammatory cytokines may cause direct tissue damage.5 It also leads to impaired immunity and therefore to the inability to react to further infections,6 as well as alter normal immune surveillance.7 By attenuating this systemic overflow of inflammatory mediators at the early phase of sepsis, these blood purification techniques could modulate the host inflammatory response and restore immunological homeostasis.2,3 However, the ability to remove cytokines using standard continuous hemofiltration with conventional filters and flow rates has proven suboptimal or even deleterious effects.8,9 Therefore, hybrid blood purification techniques using various solute transport principles and modified filters are currently in development.10–12 Coupled plasma filtration adsorption (CPFA) is one of these hybrid therapies, which is based on adsorption of cytokines on a specific resin cartridge.13,14 The plasma is first separated from the blood using a plasma filter. Then, it circulates through a hydrophobic styrenic resin cartridge, which has a high affinity for many inflammatory mediators. After a nonselective adsorption of cytokines on the resin sorbent, plasma returns to the blood where a hemofilter is set up for renal support (Figure 1). Thus, CPFA is considered an adjuvant blood purification therapy for septic shock.13

Figure 1

Figure 1

In critically ill patients, numerous parameters affect antibiotic pharmacokinetics. Acute changes in volume of distribution, organ clearance of drugs, and the pharmacologic properties of antibiotics make drug efficacy unpredictable. Therefore, monitoring of serum antibiotic concentrations is often necessary.15 One of the major drawbacks of blood purification techniques could be the unintended elimination of numerous beneficial molecules, such as vitamins, amino acids, nutrients, and drugs, including antibiotics.16 When such techniques are used, the removal of antibiotics by blood purification therapy must be taken into account. Although underdosing of antibiotics can result in poor infection control and an increased rate of antibiotic resistance, overdosing can result in toxicity.17 The efficacy of time-dependant antibiotics (like β-lactams) requires serum and tissue antibiotic concentrations above the minimal inhibitory concentration (MIC) of the pathogen for extensive periods.18 The adjustment of antibacterial dosing during blood purification therapy is crucial to achieve adequate blood levels.19 Data regarding adsorption of antibiotics during CPFA are limited.

We measured serum concentrations of all the antibiotics administered in the patients undergoing CPFA in our intensive care unit for septic shock to detect under- or overdosing during implementation of this new blood purification therapy. The aim of this retrospective study was to assess the pharmacokinetics of a variety of antibiotics during CPFA based on these samplings.

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Methods

Study Population

This retrospective study was conducted in a 10 bed intensive care unit of a teaching hospital of Lyon, France. Patients receiving antibiotics and treated with CPFA were included in the analysis. All patients presented symptoms of septic shock with multiple organ failure according to the consensus definition of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee.20 All patients experienced sepsis-induced acute kidney injury (AKI). The diagnosis of AKI was based on the Kidney Disease Improving Global Outcomes (KDIGO) classification.21 In addition to the therapies described herein, all patients received conventional treatment of septic shock, including vasopressor agents, fluid resuscitation, and early administration of broad-spectrum antibiotics. As it was a retrospective analysis of routine samples without patient identifiers, this study did not require review from Institutional Review Board, and informed consent for participation in the study was waived according to the French ethics legislation (Articles L1121-1 indent 1° and article R1121-2 of the French Public Health Code).22

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Coupled Plasma Filtration Adsorption

The vascular access for CPFA was a 13 F double lumen venous catheter inserted into either the femoral or the right jugular vein. Coupled plasma filtration adsorption was performed using a commercially available blood purification machine (LYNDA; Bellco, Mirandola, Italy) with CPFA kit (ABL 814, Bellco SpA). The CPFA kit circuit included a plasmafilter (0.5 m2 polyethersulfone, cutoff = 800 kDa; MPS 05, Bellco SpA), an adsorbent cartridge containing hydrophobic styrene resin with macroporous structure (50,000 m2/cartridge; Mediasorb; Bellco), coupled in series to a synthetic high-flux hemofilter (1.4 m2 polyethersulfone, HFT 14; Bellco) (Figure 1). Blood flow rate was set to 200 ml/min, and the plasma separation rate was set to 15% (plasma flow rate of 30 ml/min). After passing through the resin cartridge, the plasma fraction returned to the blood circulation and then entered the hemofilter. Hemofiltration was performed with an ultrafiltration flow rate of 35 ml/kg/h. Bicarbonate-buffered replacement fluid was administered with 100% postdilution. Anticoagulation was achieved via continuous intravenous infusion of unfractioned heparin. Coupled plasma filtration adsorption was performed for 8 to 10 h, and continuous venovenous hemofiltration was performed for the remainder of the day by reducing the plasma flow rate to zero. Each patient received anywhere from one to three CPFA sessions.

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Antibiotic Administration and Quantification

After a 4 g/500 mg intravenous loading dose, the combination of piperacillin–tazobactam was administrated by continuous infusion over 24 h (piperacillin 12–16 g/tazobactam 1,500–2,000 mg). Similarly, vancomycin dosing regimen was 15 mg/kg intravenous loading dose followed by 30 mg/kg/d and adjusted to maintain serum concentrations between 20 and 30 mg/L. Ceftriaxone was administered intravenously at the dose of 2 g every 24 h, cefotaxime at the dose of 1.5 g every 4 h, and ceftazidime at the dose of 2 g every 8 h. Ofloxacin was administered intravenously at the dose of 200 mg every 12 h and ciprofloxacin at the dose of 400 mg every 12 h.

At initiation, 2, 4, and 8 h of each CPFA sessions, five samples were simultaneously taken from inflow line, outflow line, pre-cartridge, post-cartridge, and ultrafiltrate sampling ports (Figure 1). Vancomycin concentrations were measured using a homogeneous particle-enhanced turbidimetric inhibition immunoassay on the Dimension Xpand system (Siemens diagnostic, Erlangen, Germany). Ceftazidime, ceftriaxone, cefotaxime, piperacilline, and tazobactam concentrations were determined by high-performance liquid chromatography (HPLC) with diode array ultraviolet detection. Ofloxacin and ciprofloxacin were analyzed by HPLC with fluorescence detection.23,24 Optimization of these analytical methods was performed. These optimized assays were validated in terms of specificity, linearity, accuracy, and precision.25 For all methods, the intra-assay and interassay variations were <15%. Overall, assay accuracy was in a range of 80% and 110%.

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Pharmacokinetics Analysis

Adsorbent extraction ratio (AER) of each antibiotic on the resin cartridge was calculated by using the following equation: AER = (CPRE − CPOST)/CPRE, with CPRE as the concentration from the pre-cartridge sample (site 3) and CPOST, the concentration from the post-cartridge sample (site 4). Coupled plasma filtration adsorption total extraction ratio (CER) was calculated as (CA − CV)/CA, with CA as the inflow (“arterial”) line concentration (site 1) and CV the outflow (“venous”) line concentration (site 2). CUF is the concentration from the ultrafiltrate (site 5).

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Statistical Analysis

Results are expressed as mean ± standard deviation (SD) for variables with normal distribution. Normality of the data was assessed with a Shapiro–Wilk test. Repeated measures analysis of variance was used to assess the differences of the dependent variables with a normal distribution over time. Tukey post hoc analyses were performed when necessary. p < 0.05 was considered statistically significant. Statistical analysis was performed using Statistica software (version 10.0; StatSoft Inc, Tulsa, OK).

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Results

Results from five consecutive patients were analyzed. Upon initiation of CPFA treatment, all patients presented AKI stage 3 of the KDIGO classification. The demographic characteristics, the causes of infection, the antibacterial treatment administered to each patient, and the outcome are reported in Table 1. The number of series of draws obtained from each antibiotic is summarized in Table 2. Only one set of data was obtained for ceftriaxone, ceftazidime, and ofloxacin. There were no adverse effects attributed to the use of these antibacterial treatments in this study population.

Table 1

Table 1

Table 2

Table 2

The mean (± SD) AER for piperacillin, vancomycin, and tazobactam at 2, 4, and 8 h after initiation of CPFA are presented in Figure 2. The AER of piperacillin at 2 h (95.4 ± 6.9%) was significantly different compared with the AER at 4 h (29.9 ± 51.8%) (p = 0.03) and 8 h (6.3 ± 51.8%) (p = 0.008). The AER of vancomycin at 2 h (99.6 ± 0.9%) was significantly different compared with the AER at 8 h (−30.2 ± 25.5%) (p = 0.02). The AER of tazobactam were not significantly different over time (7.2 ± 15.0% at 2 h; 4.5 ± 8.2% at 4 h, and 0.8 ± 2.0% at 8 h) (Figure 2).

Figure 2

Figure 2

The serum concentrations of piperacillin, vancomycin, and tazobactam at initiation of CPFA were, respectively, 148.9 ± 58.1, 18.3 ± 16.0, and 15.5 ± 6.6 mg/L. There were no significant changes in mean serum concentrations of piperacillin, vancomycin, and tazobactam over time (Table 3). The CER of piperacillin, vancomycin, and tazobactam were not significantly different over time (respectively: p = 0.06, p = 0.4, and p = 0.6) (Table 3).

Table 3

Table 3

The pharmacokinetic parameters and concentrations obtained from cefotaxime, ceftriaxone, ceftazidime, ciprofloxacin, and ofloxacin are presented in Table 3. Means and SD were not provided because of limited sample sizes.

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Discussion

The major findings of our study are that adsorption of piperacillin and vancomycin is approximately 100% on CPFA resin cartridge during the first 2 h of the treatment (Figure 2). However, this adsorption decreases significantly over time and, overall, has no effect on serum concentrations during the treatment (Table 3). Tazobactam has a low and relatively constant adsorption rate (<20%) during CPFA treatment. The significant decrease in AER of piperacillin and vancomycin, as well as a negative AER observed after 2, 4, or 8 h of CPFA treatment, suggests that piperacillin and vancomycin adsorption is saturable and reversible over time, leading to a release of these antibiotics from the resin. Despite the limited number of measures obtained, fluoroquinolones (ofloxacin and ciprofloxacin) seem to be highly adsorbed on the resin cartridge. Minimal adsorption was found for the three cephalosporins.

Biological effect of CPFA on immune function has been demonstrated in experimental and clinical studies. In vitro and in vivo adsorption of several cytokines (tumor necrosis factor-α, interleukin [IL]-6, IL-8, IL-10) has been established.26,27 Interestingly, several studies also demonstrated that CPFA could restore leukocyte responsiveness altered in sepsis (immunoparalysis).28,29 Despite this biological rationale for the use of sorbents in blood purification and some promising results in preclinical and small clinical studies, beneficial evidence from large multicenter studies is still lacking.13 In a rabbit model of septic shock, CPFA was reported to increase survival.30 Two clinical trials demonstrated improvement in hemodynamic and respiratory parameters.29,31 More recently, CPFA was compared with other blood purification techniques in animal and clinical studies. An electrophysiological study of cardiac repolarization in a pig model of endotoxemic shock failed to demonstrate a significant change in delay repolarization, unlike continuous hemofiltration.32 In addition, Sykora et al.33 recently reported that CPFA failed to reverse sepsis-induced microvascular disturbance, systemic inflammation, and hemodynamic changes in a pig model of peritonitis. Finally, in a small clinical study, Lentini et al.34 reported no difference in hemodynamic effects between pulse high-volume hemofiltration and CPFA.

Beyond these controversial data from the literature, clinical safety of CPFA must be addressed. One essential issue of blood purification techniques is the potential deleterious consequence of removing important molecules such as nutriments or drugs, especially antibiotics.19 Although there was a trend toward lower serum concentrations for piperacillin during the first 2 h of CPFA, serum concentrations remained higher than four times the MIC for Pseudomonas aeruginosa (>64 mg/L) at all time-points. However, this clinical target was not achieved for ceftazidime using the described dosing regimen. The target of 20 to 30 mg/L of serum vancomycin concentration was not achieved in a large proportion of patients from the beginning of the CPFA session and at each time-point during the study. This highlights the importance of antibacterial serum concentration monitoring in intensive care, especially if a continuous extracorporeal blood purification therapy is performed. Several factors can explain why we did not observe a statistically significant decrease in antibiotics serum levels over time with the use of CPFA, despite the occurrence of adsorption onto the sorbent. Besides the small size of the cohort and the variability of the data, the low plasma separation rate of 15% and the fact that adsorption was limited to the first hours of therapy most likely limited the quantity of antibiotics captured onto the sorbent.

Our study has several limitations. First, as just mentioned, we treated a relative small number of patients using CPFA in our institution. As a consequence, there is a possibility of imprecision in determining the AER for each antibiotic. In particular, cefotaxime, ceftriaxone, ceftazidime, ciprofloxacin, and ofloxacin pharmacokinetic parameters should be interpreted with caution. Second, as our study was purely observational, timing between administration of antibiotics and initiation of CPFA was not controlled. Thus, time to reach optimal and steady state antibacterial serum concentrations may not have been sufficient in all cases. Indeed, antibiotic measurements were performed at the early phase of therapy. This could also have contributed to the elevated variability of the data. Notwithstanding such factors, antibiotics and CPFA were both required urgently, and no guidelines are currently available for timing of initiation of a blood purification therapy. Indeed, blood purification techniques are often initiated without regard for the pharmacodynamics of the antibiotics. Third, high antibiotics regimen and administration used during continuous renal replacement therapy (CRRT) in this study may vary from recommended regimens for patients with renal failure. However, increasing evidence supports the use of “normal” doses in critically ill patients treated with CRRT for several antibiotics such as β-lactams to avoid underdosing.35,36 Continuous administration of piperacillin–tazobactam was also chosen to maximize drug exposure of this time-dependent antibiotic.37 As a consequence, the use of these antibiotic regimens could have led to acceptable serum concentrations of piperacillin, tazobactam, and vancomycin.

In experimental conditions, various plasma flow rates through the resin cartridge have been tested. A low flow of plasma allows for a longer contact time with the sorbent and therefore an enhanced adsorption property.38 The resin used for CPFA was chosen from different sorbents because of its high adsorption capacity for cytokines.39 In clinical studies and bedside application of CPFA, the same low plasma flow rate with a 15% to 20 % plasma separation rate from blood flow was fixed when adsorption of cytokines were measured.29,31,40 For all our study patients, we maintained the same blood and plasma flow rates. Consequently, variations in the adsorption capacity of antibiotics related to different flow rates through the resin cartridge have been avoided.

To our knowledge, this is the first study assessing the removal of antibiotics during CPFA in patients with septic shock. Based on these results, we suggest that piperacillin/tazobactam and vancomycin should be administered during CPFA treatment without reduction of dose. However, our findings are still insufficient to establish the optimal dosing regimen of these antibacterial agents and to draw conclusions about safety of these antibiotics during CPFA. Adequate serum concentrations of vancomycin should be verified before the initiation of CPFA. Moreover, an antibacterial serum concentration monitoring should be performed during CPFA and other CRRT as conventional doses of antibiotics could result in underdosing as recently suggested by Seyler et al.36 A better understanding of the optimal antibacterial dosing regimens during CPFA requires further investigation.

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Conclusions

In this study, piperacillin, tazobactam, and vancomycin, administered during CPFA, using the described dosing regimens, achieved acceptable serum concentrations, despite adsorption on the resin cartridge. Monitoring of antibiotics serum concentrations remains essential to avoid antibiotics underdosing. Further studies are warranted not only to confirm and validate these antibiotic pharmacokinetics findings but also to, more generally, define the precise role of this adjuvant, immunomodulatory extracorporeal treatment in the management of sepsis.

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Acknowledgments

The authors thank Kathryn Arbogast for her technical assistance.

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References

1. Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34:344–353
2. Honoré PM, Joannes-Boyau O, Collin V, Boer W, Jennes S. Continuous hemofiltration in 2009: What is new for clinicians regarding pathophysiology, preferred technique and recommended dose? Blood Purif. 2009;28:135–143
3. Rimmelé T, Kellum JA. Clinical review: Blood purification for sepsis. Crit Care. 2011;15:205
4. Rimmelé T, Kellum JA. High-volume hemofiltration in the intensive care unit: A blood purification therapy. Anesthesiology. 2012;116:1377–1387
5. Suntharalingam G, Perry MR, Ward S, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006;355:1018–1028
6. Hotchkiss RS, Coopersmith CM, McDunn JE, Ferguson TA. The sepsis seesaw: Tilting toward immunosuppression. Nat Med. 2009;15:496–497
7. Peng Z, Singbartl K, Simon P, et al. Blood purification in sepsis: A new paradigm. Contrib Nephrol. 2010;165:322–328
8. Cole L, Bellomo R, Hart G, et al. A phase II randomized, controlled trial of continuous hemofiltration in sepsis. Crit Care Med. 2002;30:100–106
9. Payen D, Mateo J, Cavaillon JM, Fraisse F, Floriot C, Vicaut E. Impact of continuous venovenous hemofiltration on organ failure during the early phase of severe sepsis: A randomized controlled trial. Crit Care Med. 2009;37:803–810
10. Cruz DN, Antonelli M, Fumagalli R, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: The EUPHAS randomized controlled trial. JAMA. 2009;301:2445–2452
11. Joannes-Boyau O, Honore PM, Boer W, Collin V. Are the synergistic effects of high-volume haemofiltration and enhanced adsorption the missing key in sepsis modulation? Nephrol Dial Transplant. 2009;24:354–357
12. Rimmelé T, Assadi A, Cattenoz M, et al. High-volume haemofiltration with a new haemofiltration membrane having enhanced adsorption properties in septic pigs. Nephrol Dial Transplant. 2009;24:421–427
13. Page M, Rimmelé T. [Coupled plasma filtration adsorption: rationale and perspectives in septic shock]. Can J Anaesth. 2008;55:847–852
14. Bellomo R, Tetta C, Ronco C. Coupled plasma filtration adsorption. Intensive Care Med. 2003;29:1222–1228
15. Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009;37:840–851
16. Bellomo R, Tan HK, Bhonagiri S, et al. High protein intake during continuous hemodiafiltration: Impact on amino acids and nitrogen balance. Int J Artif Organs. 2002;25:261–268
17. Roberts JA, Kruger P, Paterson DL, Lipman J. Antibiotic resistance—What’s dosing got to do with it? Crit Care Med. 2008;36:2433–2440
18. Taccone FS, Laterre PF, Dugernier T, et al. Insufficient beta-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14:R126
19. Choi G, Gomersall CD, Tian Q, Joynt GM, Freebairn R, Lipman J. Principles of antibacterial dosing in continuous renal replacement therapy. Crit Care Med. 2009;37:2268–2282
20. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250–1256
21. KDIGO AKI Work Group. . KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1–138
22. Claudot F, Alla F, Fresson J, Calvez T, Coudane H, Bonaïti-Pellié C. Ethics and observational studies in medical research: Various rules in a common framework. Int J Epidemiol. 2009;38:1104–1108
23. Cañada-Cañada F, Espinosa-Mansilla A, Muñoz de la Peña A. Separation of fifteen quinolones by high performance liquid chromatography: Application to pharmaceuticals and ofloxacin determination in urine. J Sep Sci. 2007;30:1242–1249
24. Ocampo AP, Hoyt KD, Wadgaonkar N, Carver AH, Puglisi CV. Determination of tazobactam and piperacillin in human plasma, serum, bile and urine by gradient elution reversed-phase high-performance liquid chromatography. J Chromatogr. 1989;496:167–179
25. Nicolas O, Farenc C, Bressolle F. [A strategy for validation of bioanalytical methods to support pharmacokinetic and toxicological studies]. Ann Toxicol Anal. 2004;16:118–127
26. Cole L, Bellomo R, Davenport P, et al. The effect of coupled haemofiltration and adsorption on inflammatory cytokines in an ex vivo model. Nephrol Dial Transplant. 2002;17:1950–1956
27. Tetta C, Cavaillon JM, Schulze M, et al. Removal of cytokines and activated complement components in an experimental model of continuous plasma filtration coupled with sorbent adsorption. Nephrol Dial Transplant. 1998;13:1458–1464
28. Mao HJ, Yu S, Yu XB, et al. Effects of coupled plasma filtration adsorption on immune function of patients with multiple organ dysfunction syndrome. Int J Artif Organs. 2009;32:31–38
29. Ronco C, Brendolan A, Lonnemann G, et al. A pilot study of coupled plasma filtration with adsorption in septic shock. Crit Care Med. 2002;30:1250–1255
30. Tetta C, Gianotti L, Cavaillon JM, et al. Coupled plasma filtration-adsorption in a rabbit model of endotoxic shock. Crit Care Med. 2000;28:1526–1533
31. Formica M, Olivieri C, Livigni S, et al. Hemodynamic response to coupled plasmafiltration-adsorption in human septic shock. Intensive Care Med. 2003;29:703–708
32. Stengl M, Sykora R, Chvojka J, et al. Differential effects of hemofiltration and of coupled plasma filtration adsorption on cardiac repolarization in pigs with hyperdynamic septic shock. Shock. 2010;33:101–105
33. Sykora R, Chvojka J, Krouzecky A, et al. Coupled plasma filtration adsorption in experimental peritonitis-induced septic shock. Shock. 2009;31:473–480
34. Lentini P, Cruz D, Nalesso F, et al. [A pilot study comparing pulse high volume hemofiltration (pHVHF) and coupled plasma filtration adsorption (CPFA) in septic shock patients]. G Ital Nefrol. 2009;26:695–703
35. DelDot ME, Lipman J, Tett SE. Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltration. Br J Clin Pharmacol. 2004;58:259–268
36. Seyler L, Cotton F, Taccone FS, et al. Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy. Crit Care. 2011;15:R137
37. Roberts JA, Kirkpatrick CM, Roberts MS, Dalley AJ, Lipman J. First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis. Int J Antimicrob Agents. 2010;35:156–163
38. Formica M, Inguaggiato P, Bainotti S, Wratten ML. Coupled plasma filtration adsorption. Contrib Nephrol. 2007;156:405–410
39. Tetta C, Cavaillon JM, Camussi G, Lonnemann FG, Brendolan A, Ronco C. Continuous plasma filtration coupled with sorbents. Kidney Int Suppl. 1998;66:S186–S189
40. Page M, Hayi-Slayman D, Ber CE, et al. [Use of coupled plasma filtration adsorption for septic shock treatment]. Ann Fr Anesth Reanim. 2007;26:990–993
Keywords:

coupled plasma filtration adsorption; septic shock; blood purification; antibiotic; pharmacokinetics; piperacillin; vancomycin

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