Haemodynamic effects of arteriovenous and venovenous haemofiltration in piglets

The aim of this study was to compare the early haemodynamic effects of continuous arteriovenous haemofiltration (CAVH) with those of continuous venovenous haemofiltration(CVVH) in normal and endotoxic piglets, within the framework of a two-period cross-over trial. Sixteen domestic piglets (weight 6–18 kg) underwent 1 h of CAVH followed by 1 h of CVVH or 1 h of CVVH followed by 1 h of CAVH. Six were pre-treated with a graded endotoxin infusion to simulate clinical sepsis. The main measurements included: heart rate; mean arterial (MAP), pulmonary artery, central venous and pulmonary artery occlusion pressures; thermodilution cardiac output; and calculated systemic (SVRI) and pulmonary vascular resistance indexes. Each measurement was performed immediately before and 30 min after commencement of each technique of filtration. Commencement of haemofiltration in normal piglets caused minimal haemodynamic effects. In endotoxic piglets, commencement of filtration, whether CAVH or CVVH, caused a haemodynamic change which was significantly more pronounced in the first filter (SVRI –39%, MAP –32%) than the second filter (SVRI +22%, MAP +0.9%) (SVRI,P=0.01, first filter vs. second) (MAP,P=0.009 first filter vs. second). In conclusion, there were no significant differences between the early haemodynamic effects of CAVH and CVVH in normal or endotoxic piglets. The haemodynamic effects of either technique may become more significant in the presence of sepsis.     

Pharmacokinetics of antimicrobial agents in anuric patients during continuous venovenous haemofiltration

BACKGROUND.: The optimal drug dosing in anuric patients undergoing continuoushaemofiltration is a difficult task. More pharmacokinetic datais needed to derive practical guidelines for dosage adjustments. METHODS.: Drug elimination of various antimicrobial agents (amikacin,amoxycillin, ceftazidime, ciprofloxacin flucloxacillin, imipenem,netilmicin, penicillin G, piperacillin, sulphamethoxazole, tobramycin,vancomycin) was studied in 24 patients with acute renal failuretreated by pump-assisted continuous venovenous haemofiltration(CVVH). Concentrations of serial blood and ultrafiltrate sampleswere determined by HPLC or by fluorescence polarization immunoassay.Total body clearance (CL) and haemofilter clearance (CL_f) rateswere determined by standard model-independent equations. Datafrom published literature on fractions not bound to proteins(f_u), non-renal drug clearance fractions (Q_o) and normal clearancevalues (CL_n) were used to derive a pharmacokinetic model, takinginto account drug removal by ultrafiltration and by non-renalclearance. RESULTS.: A total of 37 treatment periods was studied. Blood flow throughthe haemofilters was 100 ml/min resulting in an average ultrafiltrateflow rate (UFR) of 13.2±4.6 (range 3.2–22.1) ml/min.Acceptable correlations of calculated and measured haemofilterclearances and total body clearances were obtained. CONCLUSIONS.: Total body clearance in anuric patients during CVVH is predictablefrom drug properties, which are generally known. The individualdosage requirements may be calculated by multiplying Q_o+f_u UFR/CL_nwith the dose considered appropriate in the absence of renalimpairment.     

Serum IL-6 and IL-1-ra with sequential organ failure assessment scores in septic patients receiving high-volume haemofiltration and continuous venovenous haemofiltration

AIM: Sepsis is characterized by an uncontrolled release of pro-inflammatory and anti-inflammatory mediators leading to immunoparalysis, cellular and humoral dysfunction, multiorgan dysfunction and death. This study evaluated the efficacy of high-volume haemofiltration (HVHF) compared with continuous venovenous haemofiltration (CVVH) in removing these inflammatory mediators. Clinical responses were assessed with the sequential organ failure assessment (SOFA) score. METHODS: Septic patients with an end-organ dysfunction or septic shock were randomized to receive 6 h of CVVH (ultrafiltration dose of 2 L/h equivalent to about 35 mL/kg per hour or HVHF (ultrafiltration dose of 100 mL/kg per hour or 6 L/h, whichever was higher). The sequential organ failures were scored for the 24 hours preceding recruitment; at day 1, day 7, at discharge from the intensive care unit and at hospital discharge. RESULTS: Thirty-three patients were enrolled. Fifteen received HVHF and 18 received CVVH. The serum IL-6 levels (pg/mL) at baseline were similarly elevated in both groups (P = 0.745). The HVHF group showed a significant reduction after 6 h of treatment with a median interquartile range (IQR) of 20.62 (49.21) pg/mL (P = 0.025) with no similar result in the CVVH group. Non-survivors showed a higher baseline serum IL-6 compared with the survivors (median (IQR) 172.31 (261.34) vs 58.9 (104.21), P = 0.044). In the HVHF group there was a positive association between the IL-6 levels at 6 h with the SOFA scores at day 1 (r = 0.392, P = 0.001) but not at day 7. After 6 h of treatment in the HVHF group there was a direct correlation between the IL-6 levels and number of hospital days (r = 0.90, P = 0.040). The maximum SOFA scores were persistently recorded before treatment. The SOFA scores reduced in both groups from baseline to day 7 (HVHF P = 0.048; CVVH P = 0.006). The SOFA scores at day 1 is significantly higher in the non-survivors compared with the survivors (P = 0.038). CONCLUSIONS: High-volume haemofiltration at 6 L/h may seem to successfully remove some inflammatory cytokines in septic patients. The improvement in the SOFA scores at day 7 promises benefit of continuous renal replacement therapy in septic patients, but after 20 days this effect may be lost. In addition, the baseline serum IL-6 and IL-1-ra were independent predictors of a poor outcome as reflected by the higher SOFA scores at day 1.     

Solute clearances during continuous venovenous haemofiltration at various ultrafiltration flow rates using Multiflow-100 and HF1000 filters.

BACKGROUND: In continuous venovenous haemofiltration (CVVH), high ultrafiltration rates provide survival benefits in acute renal failure. This study measured clearances obtained at ultrafiltration rates of up to 4.5 l/h. METHODS: Clearances of small solutes (urea, creatinine, phosphate and urate) and of beta(2)-microglobulin (beta(2)-M) were measured during CVVH. Five preset Multiflow-100 (M-100) and five HF1000 hollow-fibre filters were compared. For the M-100, clearances obtained by haemofiltration were compared with those obtained by haemodiafiltration at similar total effluent rates from a previous study. RESULTS: For small solutes, the effluent to plasma ratio (E/P) remained close to 1.0 at all ultrafiltration rates; filter clearances were thus equal to Quf for both filters. Increasing Quf from 1.0 to 4.5 l/h did not significantly modify E/P. Convective clearances of beta(2)-M were lower than those obtained for small solutes. For the M-100, average beta(2)-M E/P was 0.62+/-0.10 and did not significantly change while increasing Quf. For the HF1000, average beta(2)-M E/P were significantly lower compared with the M-100 (0.42+/-0.09 at 1.0 l/h) and decreased progressively to 0.26+/-0.06 while increasing Quf to 4.5 l/h. With pre-dilution, progressive decreases in clearances delivered to patients were observed reaching 40% at a Quf rate of 4.5 l/h. There was no clinically significant adsorption of beta(2)-M. For the M-100, at similar total effluent flow rates, clearances delivered to patients using haemodiafiltration were significantly higher for small solutes but lower for beta(2)-M in comparison to haemofiltration only. CONCLUSIONS: Filter clearance for small solutes equalled Quf at evaluated rates. At high ultrafiltration rates there was significant loss of clearances with pre-dilution. At similar total effluent rates with the use of pre-dilution, haemodiafiltration is superior to haemofiltration for small solute clearance but inferior for beta(2)-M.     

Haemodynamics and electrolyte balance: a comparison between on-line pre-dilution haemofiltration and haemodialysis.

BACKGROUND: An important advantage of convective therapies is improved vascular reactivity. However, it is not well known whether the vascular response during convective therapies remains superior when compared to haemodialysis (HD) with an adjusted temperature of the dialysate. It has also been suggested that convective therapies may impair small electrolyte removal through an effect on the Donnan equilibrium. In the present study, we compared the haemodynamic response and small electrolyte removal between pre-dilution on-line haemofiltration (HF) and HD procedures. METHODS: Cardiac output (CO), central blood volume (CBV) and peripheral vascular resistance (PVR) were assessed, using the saline dilution technique, in 12 stable patients during HF and HD with two different temperatures of the dialysate [36.5 and 35.5 degrees C (HD(36.5) and HD(35.5))]. Balances for sodium, potassium, calcium and conductivity were assessed using total dialysate/filtrate collections. Target filtration volume for HF was 1.2 times body weight. The temperature of the infusate was 36.5 degrees C. RESULTS: The change (Delta) in CBV was less during HD with a dialysate temperature of 35.5 degrees C (-0.03+/-0.14 l; P<0.05) compared to HF (-0.16+/-0.05 l) and HD(36.5) (-0.11+/-0.14 l), but the other haemodynamic parameters did not differ between the studied techniques. DeltaPVR was significantly related to DeltaCBV (r = -0.46; P<0.01), whereas DeltaCBV was related to ultrafiltration rate (r = -0.34; P = 0.05). DeltaCO was related to DeltaCBV (r = 0.62; P<0.001). Solute balances did not differ between HF and HD. CONCLUSION: Using the saline dilution method, no difference in the change in CO and PVR was observed between on-line HF vs HD(36.5) and HD(35.5). Only CBV declined to a significantly lesser degree during HD(35.5), although absolute differences were small. Changes in the other haemodynamic variables appeared more dependent upon the degree and rapidity of fluid removal than upon the treatment modality. No difference in small electrolyte balance was observed between HF and HD, suggesting that ionic removal is not impaired during on-line HF.     

Concurrent centrifugation plasmapheresis and continuous venovenous hemodiafiltration

Continuous venovenous hemofiltration/hemodiafiltration (CVVH/D) is commonly used to provide renal replacement therapy for critically ill patients who are hemodynamically unstable. Occasionally, the addition of plasmapheresis therapy is necessary for some conditions, including immune-mediated acute renal failure, sepsis, fulminant hepatic failure, and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Most tertiary care facilities provide centrifugation plasmapheresis instead of membrane plasmapheresis, because of the requirement for both therapeutic plasma exchange and pheresis of cellular blood products. We report a new technique where centrifugation plasmapheresis and CVVHD (P-CVVHD) are combined and used concurrently. Blood from the patient was concurrently filtered utilizing a Hospal BSM 22 machine with a Multiflow 60 hemofilter and a Cobe Spectra continuous cell separator in a parallel configuration. P-CVVHD is technically possible and can be used for long periods of time with limited risks. There may be advantages to P-CVVHD compared with discontinuous combined CVVH/D and plasmapheresis therapy. Received: 10 June 1998 / Revised: 4 January 1999 / Accepted: 6 January 1999     

Effects of continuous haemofiltration vs intermittent haemodialysis on systemic haemodynamics and splanchnic regional perfusion in septic shock patients: a prospective, randomized clinical trial.

BACKGROUND: Parameters of splanchnic regional perfusion, like intramucosal pH (pHi) and pCO(2) (pCO(2)i), may predict outcome in septic shock patients. Continuous venovenous haemofiltration (CVVH) has been considered beneficial in haemodynamically unstable septic shock patients. In a prospective, randomized, clinical study, we investigated whether CVVH, in comparison to intermittent haemodialysis (IHD), is able to improve splanchnic regional perfusion in critically ill patients. METHODS: Thirty septic shock patients with acute renal failure were randomized to either CVVH (n=20) or IHD (n=10) groups for renal replacement therapy. Patient characteristics at baseline were not different in terms of severity of illness (APACHE II scores), haemodynamics, and pHi/pCO(2)i values. Systemic haemodynamics, oxygen transport variables, and splanchnic regional perfusion parameters were measured at 0.5, 2, 4 and 24 h after initiation of renal replacement therapy. There were no major changes in vasopressor support throughout the 24-h study period. RESULTS: In contrast to IHD, CVVH caused a decrease in heart rate (-3+/-11 vs +9+/-8/min, P<0.01) and an increase in systolic blood pressure (+12+/-1 vs -5+/-17 mmHg, P<0.05) after 2 h. After 24 h, increased systemic vascular resistance was found in the CVVH group in comparison with the IHD group (+312+/-755 vs -29+/-89 dyne/cm(5), P<0.05) and was accompanied by a decrease in cardiac output (-1.54+/-1.4 vs -0.25+/-0.9 l/min, P<0.01). However pHi values remained constant throughout the 24-h study period in both groups and were not different between the groups (CVVH 7.19+/-0.1 vs IHD 7.19+/-0.1, n.s.) as did the pCO(2)i values (CVVH +7+/-17 vs IHD 0+/-15 mmHg, n.s.) and pCO(2) gap values (CVVH +6+/-15 vs IHD +5+/-12 mmHg, n.s.). CONCLUSIONS: Despite different changes of systemic haemodynamics between CVVH and IHD, CVVH did not improve parameters of splanchnic regional perfusion like pHi, pCO(2)i or pCO(2) gap in septic shock patients.     

The impact of long-term haemofiltration (continuous veno-venous haemofiltration) on cell-mediated immunity during endotoxaemia

BACKGROUND: Increased survival with high-volume continuous veno-venous haemofiltration (CVVH) has been demonstrated in critically ill patients. This may be the result of intensified blood purification or an effect on the immune system. We hypothesized that CVVH modifies the cell-mediated immunity. We investigated the effect of high-volume CVVH for 24 h on the cell-mediated immunity following endotoxin infusion. METHODS: Thirty pigs were divided into three groups. Ten pigs received 30 microg/kg of Escherichia coli endotoxin. These pigs were treated with CVVH (replacement 35 ml/kg/h) over the following 24 h. Ten pigs received the same bolus of endotoxin and ten pigs served as a control group. The adhesion molecules CD18, CD44 and CD62L and the ability to respond with an oxidative burst were measured. The number of neutrophils was counted in blood and lung tissue. The lymphoproliferative response and cytokines interleukin-6 and interleukin-10 were measured. RESULTS: The infusion of endotoxin was followed by initial granulocytopenia and, later, granulocytosis, activation of CD18 and CD62L, and increased oxidative burst. The cytokine level was increased. CVVH had no effect on the adhesion molecules or cytokine level and did not reduce the number of granulocytes in the lung significantly. CVVH, however, reduced the oxidative burst activity of neutrophils after 2 h of treatment. CONCLUSION: In the first few hours after endotoxaemia, high-volume CVVH reduced the oxidative burst activity of neutrophils. However, in the long term, CVVH was unable to modify the endotoxin-induced changes in cell-mediated immunity.     

Procalcitonin and proinflammatory cytokine clearance during continuous venovenous haemofiltration in septic patients

Procalcitonin (PCT), interleukin-6 (IL-6), tumour necrosis factor a (TNFalpha), and interleukin-1beta (IL-1beta) are important clinical prognostic markers in ICU septic patients. The goal of the study was to determine whether continuous venovenous haemofiltration (CWH), using an AN69 haemofilte, leads to elimination of PCT, TNFalpha, IL-6 and IL-1beta in 13 septic patients with multi-organ failure. At the start of haemofiltration (0), 6 and 12 hours the mean afferent plasma concentration +/- SD of PCT (10.1 +/- 9.1, 7 +/- 6, 5.9 +/- 5.7 ng/ml), IL-6 (804.6 +/- 847.6, 611.7 +/- 528.4, 575.2 +/- 539.2 pg/ml), and that of TNFalpha (4.5 +/- 2.6, 4 +/- 3.1, 3.8 +/- 2.9 pg/ml) significantly declined during CVVH. The efferent plasma concentrations were significantly lower than the corresponding afferent concentrations. PCT; IL-6 and TNFalpha were detectable in the ultrafiltrate of all patients. IL-1beta was only detectable in the plasma of eight patients and the ultrafiltrate of five patients. The plasma clearance of PCT, IL-6 and TNFalpha significantly decreased after 12 hours as a result of a decline in the adsorptive elimination of the mediators due to progressive membrane saturation. We demonstrated that if PCT, IL-6 and TNFalpha are used as clinical prognostic markers in septic patients who are treated with CWIH using an AN69 membrane, one should be aware that their plasma level could be modified by the therapy. In addition CWH could represent an appropriate tool to remove a broad spectrum of proinflammatory mediators, if such removal is required in septic patients.     

Predilution haemofiltration--the Second Sardinian Multicentre Study: comparisons between haemofiltration and haemodialysis during identical Kt/V and session times in a long-term cross-over study.

BACKGROUND: The potential superiority of various renal replacement treatment modalities consisting largely of convective mass transfer as opposed to primarily diffusive mass transfer, is still a matter of debate. The objective of the present study was to evaluate acute and long-term clinical effects of varying degrees of convection and diffusion in a group of 24 clinically stable patients with end-stage renal disease. METHODS: The patients were prospectively assigned to three consecutive treatment schedules of 6 months each: phase I (HF1) (on-line predilution haemofiltration)-->phase II (HD) (high-flux haemodialysis)-->phase III (HF2; as phase I). We used the AK100/200 ULTRA monitor (Gambro), which prepares ultrapure dialysis fluid for HD and sterile, pyrogen-free substitution solution for HF. The membrane (polyamide), fluid composition, and treatment time were the same on HF and HD. The targeted equilibrated Kt/V was 1.2 for both treatment modes, creating a similar urea clearance. RESULTS: Fifteen patients, mean age 62.8+/-8.4 years, completed the study according to the above conditions. Urea kinetics, nutritional parameters, and dry weight were similar in the three periods. The frequency of intra-treatment episodes of hypotension/patient/month was significantly lower on HF1 (1.24) and HF2 (1.27) than on HD (1.80) (P<0.04). It decreased progressively on HF1, then increased on HD, and decreased again during HF2. Patients had fewer muscular cramps on HF than on HD (P<0.03) and required significantly less saline and plasma expander during HF than HD sessions. The prevalence of inter-treatment symptoms, including fatigue and hypotension, was lower on HF than on HD (score difference P=0.04). Quality of life, determined by the Laupacis method in all three periods, showed a tendency towards improvement during the study, reaching the best values during HF2. CONCLUSIONS: HF has a progressive stabilizing haemodynamic effect, producing a more physiological cardiovascular profile than HD. This long-term effect, observed in stable patients treated under strictly identical conditions, is probably due to the mechanism of convection, and is different from the acute effect observed mainly in unstable patients.     

Haemodynamics and cardiovascular shock

Haemodynamics is the study of blood flow around the body. The factors influencing haemodynamics are complex and include cardiac output, circulating blood volume, vessel diameter, resistance and blood viscosity. These, in turn, are interlinked and affected by factors such as exercise, posture, disease, drugs and obesity. In this article we shall explore the physiology and control of blood flow and pressure in health, moving on then to look at what happens when control mechanisms break down, resulting in cardiovascular shock.     

Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg

To cover intermediate sensitive Candida glabrata in ICU patients,fluconazole plasma peak levels at least in the range of 16–32µg/ml appear necessary for treatment. Previous studiesdid not reach these fluconazole levels under continuous veno-venoushaemofiltration (CVVHF) with dosages of 200–600 mg fluconzoledaily. In the present study, nine patients simultaneously requiringCVVHF for treatment of acute oligoanuric renal failure and antimycotictherapy of Candida septicemia received fluconazole 800 mg/day.Fluconazole plasma levels were determined to evaluate whetherthis dosage is adequate to reach the advised fluconazole levels.Patients were dialysed on two consecutive days with an ultrafiltrationrate (UF) of 1000 ml/h or 2000 ml/h, respectively, in a randomizedorder. The predilution was 800 ml/h and 1800 ml/h, respectively.The treatment was tolerated without adverse effects. All patientsreached plasma fluconazole concentrations between 16 and 32µg/ml, remaining in this range for a minimum of 1 up to24 h with a mean of 9.6 h and a UF rate of 2000 ml/h, and 15.7h with a UF rate of 1000 ml/h. So far, there are no in vivodata on the fluconazole plasma concentrations required for effectivetreatment. However, our data demonstrate, that at least thefluconazole concentrations desirable on the basis of in vitrosusceptibility testing can be reached in critically ill patientson CVVHF in an ICU setting. However, in these patients, 800mg fluconazole/day are necessary to achieve fungicidal drugconcentrations.     

Continuous arteriovenous haemofiltration in the treatment of tumour lysis syndrome

The management of tumour lysis syndrome remains problematic despite the rigorous use of preventative measures. Continuous arteriovenous haemofiltration (CAVH) is well suited to its use in both the prevention and treatment of metabolic abnormalities and renal insufficiency associated with tumour lysis. We report the successful use of CAVH in the treatment of a patient with tumour lysis syndrome.     

Beneficial effects of plasmapheresis before thymectomy on the outcome in myasthenia gravis

Objective: Since 1980, we have performed plasmapheresis before thymectomy for patients with generalized symptoms in order to protect against myasthenic crisis and to improve patient outcomes after thymectomy. The aim of this study was to evaluate an immediate and a long-term results of plasmapheresis before thymectomy for myasthenia gravis, retrospectively. Methods: Between January 1980 and December 1997, 51 patients with Osserman class IIA or IIB symptoms were treated with transsternal thymectomy. Nineteen patients (group 1) were treated with plasmapheresis before thymectomy and 32 patients (group 2) were treated with thymectomy alone. Results: In group 1, the time of plasmapheresis prior to thymectomy was 3.2±1.5. Nine (28.1%) patients in group 2 had crisis within 1 year after thymectomy as compared with only one (5.3%) patient in group 1 had crisis (p=0.049). There was no evidence of crisis within 30 days after thymectomy in group 1 and 5 (15.6%) patients in group 2 (p=0.0724). there was no postoperative death among patients in group 1. Responses to thymectomy in group 1 improved significantly, the improvement and pharmacologic remission rate had increased up to 100% and 79% at 5–7 years after operation, while the improvement and pharmacologic remission rate of group 2 had increased to 81.3% (p=0.0466 vs. group 1) and 50.0% at that time (p=0.0427 vs. group 1). Conclusions: The present study demonstrated that preoperative plasmapheresis may facilitate improved outcomes of patients with myasthenia gravis after thymectomy.     

Beneficial effects of plasmapheresis before thymectomy on the outcome in myasthenia gravis

OBJECTIVE: Since 1980, we have performed plasmapheresis before thymectomy for patients with generalized symptoms in order to protect against myasthenic crisis and to improve patient outcomes after thymectomy. The aim of this study was to evaluate an immediate and a long-term results of plasmapheresis before thymectomy for myasthenia gravis, retrospectively. METHODS: Between January 1980 and December 1997, 51 patients with Osserman class IIA or IIB symptoms were treated with transsternal thymectomy. Nineteen patients (group 1) were treated with plasmapheresis before thymectomy and 32 patients (group 2) were treated with thymectomy alone. RESULTS: In group 1, the time of plasmapheresis prior to thymectomy was 3.2 +/- 1.5. Nine (28.1%) patients in group 2 had crisis within 1 year after thymectomy as compared with only one (5.3%) patient in group 1 had crisis (p = 0.049). There was no evidence of crisis within 30 days after thymectomy in group 1 and 5 (15.6%) patients in group 2 (p = 0.0724). There was no postoperative death among patients in group 1. Responses to thymectomy in group 1 improved significantly, the improvement and pharmacologic remission rate had increased up to 100% and 79% at 5-7 years after operation, while the improvement and pharmacologic remission rate of group 2 had increased to 81.3% (p = 0.0466 vs. group 1) and 50.0% at that time (p = 0.0427 vs. group 1). CONCLUSIONS: The present study demonstrated that preoperative plasmapheresis may facilitate improved outcomes of patients with myasthenia gravis after thymectomy.     

Acid--base responses to high-volume haemofiltration in the critically ill

We have studied the acid-base and cardiorespiratory effectsof intermittent pumped high-volume venovenous haemofiltration(HVHF) using replacement fluid containing lactate as the sourceof bicarbonate in critically ill patients. We demonstrated significanthyperlactataemia throughout the procedure, but there was nodeterioration in acid-base status, haemo-dynamics, or oxygendelivery. These observations suggest that the worsening of acidosisand the hypotension that have been described with this technique[1] can be avoided by appropriate monitoring and resuscitationprior to haemofiltration, and may be due to unrecognized inadequaciesin the oxygen transport system.