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The sieving coefficient and clearance of vasopressin during continuous renal replacement therapy in critically ill children
Journal of Critical Care (2010) 25, 591–594
The sieving coefficient and clearance of vasopressin during continuous renal replacement therapy in critically ill children J. Scott Baird MD Columbia University, College of Physicians and Surgeons, Children's Hospital of New York-Presbyterian, New York, NY 10032, USA
Keywords: Hemofiltration; Vasopressin; Pediatric
Abstract Hypothesis: As vasopressin is a small peptide, its sieving coefficient (SC) and clearance (CL) during continuous renal replacement therapy may be intermediate to those for urea and β2 microglobulin (commonly used markers for small– and middle–molecular weight solutes, respectively). Methods: A prospective, minimal-risk study was undertaken of the SC and CL of vasopressin in critically ill children on the first day of continuous renal replacement therapy using AN69 membrane filters and prefilter replacement fluid. All prefilter plasma (vasopressin) samples were drawn from the arterial port after predilution. Results: Nine patients with fluid overload, renal failure, or both were recruited (median age, 14 years) during the first day of either continuous venovenous hemofiltration (n = 3) or hemodiafiltration (n = 6). Multiorgan dysfunction syndrome was present in 8 patients, and 3 were in shock (2 were receiving a vasopressin infusion). Median prefilter plasma (vasopressin) was 1.7 pg/mL, although data points were skewed: 5 patients had a low prefilter plasma (vasopressin) (b2 pg/mL), and 4 patients (including 2 receiving a continuous vasopressin infusion) had a prefilter plasma (vasopressin) between 4.2 and 56.4 pg/mL. All those with low prefilter plasma (vasopressin) had an effluent (vasopressin) less than the detection limit (0.6 pg/mL). The median SC was 1 in the 4 patients with a measurable effluent (vasopressin), and their median filter CL was 48 mL/min or 39 mL/(min 1.73 m2). Conclusions: The SC and CL of vasopressin by continuous venovenous hemofiltration or hemodiafiltration in these critically ill children were similar to values for urea. © 2010 Elsevier Inc. All rights reserved.
Solute clearance (CL) during continuous renal replacement therapy (CRRT) is dependent in part on molecular weight: small–molecular weight solutes like urea (60 d) have a high sieving coefficient (SC) and are more easily cleared than middle–molecular weight solutes like β2 microglobulin (12 kd). Of note, convective CL for both small– and middle– molecular weight solutes increases with increasing ultrafilE-mail address: [email protected]. 0883-9441/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2010.03.005
tration rate (Quf), whereas the substitution of a diffusive modality (dialysis) increases CL of small–molecular weight solutes but decreases CL of middle–molecular weight solutes [1,2]. Substances larger than β2 microglobulin have lower SC and CL; and adsorption by the hemofilter may further limit convective CL, particularly for some very dilute proteins [3]. Substances with a molecular weight at or greater than the pore size of the hemofilter membrane are not cleared by convection or diffusion.
592 The molecular weight of vasopressin is approximately 1 kd, intermediate to urea and β2 microglobulin; and its CL during continuous arteriovenous hemofiltration in adults without critical illness was high in one study (N100 mL/min) [4]. However, there are currently no data regarding vasopressin CL during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF), including in particular during critical illness at any age. This study was designed to assess both the SC and CL of vasopressin early during CRRT of critically ill children, including children receiving an infusion of vasopressin. It was hypothesized that the SC and CL of vasopressin would be intermediate to values for urea and β2 microglobulin.
1. Materials and methods A prospective study at the Morgan Stanley Children's Hospital–Columbia University College of Physicians and Surgeons was approved by the Institutional Review Board, and recruitment occurred from May 2006 through September 2008. There were no financial or personal relationships with other people or organizations that could inappropriately influence or bias this work.
1.1. Eligible patients Children older than 1 year and weighing more than 10 kg who were treated with CRRT were eligible for recruitment to this study during the first day of CRRT following informed verbal consent. The requirement to obtain written documentation of informed consent was waived, as the study was judged to involve minimal risk, based on a total blood requirement for the study of less than 1% of estimated blood volume for each patient.
1.2. Procedures Demographic, clinical, laboratory, and treatment data were obtained by review of the medical record. Organ dysfunction was determined for each patient at the initiation of CRRT, according to criteria for multiorgan dysfunction syndrome (MODS) [5]. The diagnosis of shock was based on the clinical diagnosis of shock by the patient's attending pediatric intensivist. The Gambro PRISMA device (Cobe-Gambro Healthcare, Lakewood, CO) with an AN69 polyacrylonitrile filter in a Gambro M100 filter set (surface area, 0.9 m2; cutoff value of 35-40 kd [6]; Cobe-Gambro Healthcare) was used in all patients. The CRRT mode was determined by the attending physician in the pediatric intensive care unit. All replacement fluid was infused prefilter. Patients with severe coagulopathy did not receive anticoagulation; heparin was used in the remaining patients with a goal of a circuit partial thrombo-
J.S. Baird plastin time of 60 to 80 seconds. All blood draws were taken from the hemofilter circuit: 5 mL of blood (or effluent) was drawn for each specimen in an EDTA tube. Prefilter blood was drawn from the arterial port after predilution; postfilter blood and effluent specimens were drawn from the appropriate ports. To maintain the minimal-risk status of this study and yet obtain the maximum amount of data, the SC (ie, a single prefilter blood draw of 5 mL with a concurrent effluent specimen) was assessed in children weighing 10 to 25 kg during the first day of CRRT, whereas the SC and a postfilter specimen (ie, a single blood draw of 10 mL) were assessed in children weighing 25 to 40 kg. For children weighing more than 40 kg, these specimens were drawn on day 1 and again on day 2 of CRRT. Blood or effluent was immediately centrifuged and separated; and plasma or effluent was frozen at −80°C. The Irving Center for Clinical Research at Columbia University College of Physicians and Surgeons performed all vasopressin assays using an ultrasensitive radioimmunoassay (ALPCO Diagnostics, Salem, NH).
1.3. Calculations The following formulas were used for calculations: – – – –
Quf = replacement rate + net fluid removal rate Effluent rate = Quf + dialysate rate SC = effluent (vasopressin)/prefilter (vasopressin) Filter CL = SC × effluent rate
When using CVVH, filter CL is convective CL (and effluent rate = Quf), whereas during CVVHDF, filter CL is a combination of convective and diffusive CL. To minimize blood draws and maintain minimal-risk status for this study, blood for plasma (vasopressin) levels from the arterial port before predilution were not drawn.
1.4. Statistical analysis Data are presented as medians (mean; range). Statistical tests (Spearman rank correlation) were 2-sided with significance set at P b .05. All statistical analyses were performed using InStat version 3.06 (GraphPad Software Inc, San Diego, CA).
2. Results Nine patients were recruited: age, diagnoses, the incidence of MODS and shock, and indications as well as CRRT mode are presented in Table 1. Two patients treated with a vasopressin infusion initiated before CRRT received the same vasopressin dose throughout the study (0.0003 and 0.0008 U/kg/min). Vascular access for CRRT was obtained using dual-lumen catheters (size: 7F, 9F, or 11F; MedComp
Sieving coefficient and clearance of vasopressin during CRRT Table 1
Characteristics of study population (N = 9)
Median age, y (range) Diagnosis Oncologic disease (%) Systemic lupus erythematosus (%) Renal failure (%) Other disease (%) MODS (%) Shock (%) Vasopressin infusion (%) a Catecholamine infusion (%) a CRRT indications Renal failure (%) Fluid overload (%) Renal failure + fluid overload (%) CVVH:CVVHDF Survivors (%) Deaths during the study period
14 (1-19) 3 (33) 2 (22) 2 (22) 2 (22) 8 (89) 3 (33) 2 (22) 2 (22) 1 (10) 2 (20) 6 (67) 3:6 5 (56) 0
593 patient. This last patient developed unremitting septic shock on the second day of hemofiltration coincident with the decline in prefilter plasma (vasopressin) and intermittent difficulty maintaining hemofiltration flow; she died 2 days later. Data for SC and CL on the second day of CRRT were therefore unavailable in this cohort. Serum (sodium) did not correlate with prefilter plasma (vasopressin) (P = .16 by Spearman rank correlation). Median serum (sodium) was 145 (range, 134-156) mmol/L. Four patients died during their hospitalization (2 with stem cell transplant for oncologic disease, 1 with systemic lupus erythematosus, 1 with short gut syndrome and liver failure), none during the study period.
3. Discussion
a
One patient in shock was treated both with vasopressin and a catecholamine infusion.
Duo-Flow, Harleysville, PA) via the femoral (n = 8) or subclavian (n = 1) veins, and catheter ports were used in the intended configuration only (ie, the arterial or red port was used for hemofilter circuit inflow, whereas the venous or blue port was used for hemofilter circuit outflow). The replacement fluid was a bicarbonate-saline mixture (35 mEq Na bicarbonate and 104 mEq NaCl/L), whereas the dialysate fluid was Prismasate BK 0/3.5 (Gambro). Median effluent rate was 34 (mean, 30; range, 2-68) mL/min. Median prefilter plasma (vasopressin) was 1.7 pg/mL in all 9 patients on the first day of CRRT, although data points were skewed: 5 patients had a low prefilter plasma (vasopressin) (b2 pg/mL), and 4 patients (including both patients receiving a continuous vasopressin infusion) had a prefilter plasma (vasopressin) between 4.2 and 56.4 pg/mL. There did not appear to be an association with CRRT mode (CVVH vs CVVHDF) and prefilter plasma (vasopressin): 3 patients treated with CVVHDF had low levels, and 3 did not. All those with low prefilter plasma (vasopressin) had an effluent (vasopressin) less than the detection limit (0.6 pg/mL). Median values for postfilter plasma (in 7 of 9 patients) and effluent (in all 9 patients) (vasopressin) were 1.5 (0.6-42) and b0.6 (b0.6-51) pg/mL. The median SC was 1 (mean, 1.1; range, 0.9-1.7) in the 4 patients with a measurable effluent (vasopressin), and their median filter CL was 48 (mean, 42; range, 2-71) mL/min at a median effluent rate of 38 (mean, 36; range, 2-68) mL/min; corrected for body surface area, this corresponded to an effluent rate of 39 (mean, 47; range, 7-102) mL/min/1.73 m2. Prefilter plasma and effluent (vasopressin) were also assayed on day 2 of CRRT in 4 of 9 patients: prefilter plasma (vasopressin) was 1.4, 0.6, 1.7, and 37 pg/mL on day 1 vs 1.5, 0.6, 0.8, and 12 pg/mL on day 2, respectively; effluent (vasopressin) remained less than 0.6 pg/mL for the first 3 patients on both days and fell from 38 to 7 pg/mL in the last
The SC for urea using an AN69 membrane hemofilter and prefilter replacement is near 1 [2]; as a result, its CL, either via convection [2] (CVVH) or via a combination of convection and diffusion [1] (CVVHDF), approximates the effluent rate, whereas β2 microglobulin has an SC less than 0.6 and a proportionally lower CL under similar conditions [1,2]. The results of this study suggest that, in this setting, vasopressin is filtered and cleared like urea. As the vasopressin levels in this population of critically ill children were skewed, a larger study is needed to verify if vasopressin is routinely cleared like small–molecular weight substances. Further investigation of vasopressin's SC at various effluent rates will be helpful to determine if the SC remains constant: Brunet et al [1] found a variable SC for β2 microglobulin that increased in a nonlinear fashion with increasing Quf. If the filter consistently sieves all of the vasopressin presented to it (SC = 1), a higher Quf would lead to increasing CL of vasopressin, whereas if sieving is dependent in part on Quf, CL would be much less effective at a lower Quf. Potential limitations to this study also include the accuracy of the vasopressin assay (particularly at the lower detection limit), possible hemofiltration access recirculation, and the lack of plasma (vasopressin) values from the arterial port before predilution. In response, values for vasopressin in several patients assayed on the first and second day of hemofiltration appeared similar (including those patients with low levels); the median postfilter vasopressin level was slightly less than the median prefilter vasopressin level; all specimens were processed immediately (thus limiting possible degradation); and prefilter plasma (vasopressin) was higher in children receiving a vasopressin infusion, as one might predict. Assay accuracy therefore appeared acceptable. Access recirculation may, in theory, affect CL during CRRT, although available data suggest that this is minimal when CRRT catheters are used—as in this study— as per recommendations [7]. Vasopressin CL assessed in this study reflects CL across the hemofilter and not CL delivered to the patient: predilution is responsible for a decrease in CL
594 delivered to the patient, as CL across the filter is always greater than total CL delivered to the patient. Measurement of plasma (vasopressin) before predilution would allow the magnitude of the difference between filter and patient CL of vasopressin to be quantified; however, filter CL of urea is similar to filter CL of vasopressin as noted above, suggesting that vasopressin is cleared by the hemofilter much like urea during CRRT. Vasopressin CL by CRRT deserves further investigation, particularly as CL during CVVH of another small peptide with hemodynamic consequences—brain natriuretic peptide —has recently been shown to lead to a significant decline in this peptide in infants [8].
References
J.S. Baird
[2]
[3]
[4]
[5]
[6] [7] [8]
[1] Brunet S, Leblanc M, Geadah D, Parent D, Courteau S, Cardinal J. Diffusive and convective solute clearances during continuous renal
replacement therapy at various dialysate and ultrafiltration flow rates. Am J Kidney Dis 1999;34:486-92. Troyanov S, Cardinal J, Geadah D, Parent D, Courteau S, Caron S, et al. Solute clearances during continuous venovenous haemofiltration at various ultrafiltration flow rates using Multiflow-100 and HF1000 filters. Nephrol Dial Transplant 2003;18:961-6. De Vriese AS, Colardyn FA, Philippe JJ, Vanholder RC, De Sutter JH, Lameire NH. Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol 1999;10:846-53. Pruszczynski W, Viron B, Mignon F, Ardaillou R. Massive plasma arginine vasopressin (AVP) removal during hemofiltration stimulates AVP secretion in humans. J Clin Endocrinol Metab 1987;64:383-6. Proulx F, Gauthier M, Nadeau D, Lacroix J, Farrell CA. Timing and predictors of death in pediatric patients with multiple organ system failure. Crit Care Med 1994;22:1025-31. Chanard J, Toupance O, Gillery P, Lavaud S. Evaluation of protein loss during hemofiltration. Kidney Int Suppl 1988;24:S114-6. Schetz M. Vascular access for HD and CRRT. Contrib Nephrol 2007;156:275-86. Ricci Z, Garisto C, Morelli S, Di Chiara L, Ronco C, Picardo S. Brain natriuretic peptide is removed by continuous veno-venous hemofiltration in pediatric patients. Interact Cardiovasc Thorac Surg 2009;9:33-6.
The sieving coefficient and clearance of vasopressin during continuous renal replacement therapy in critically ill children J. Scott Baird MD Columbia University, College of Physicians and Surgeons, Children's Hospital of New York-Presbyterian, New York, NY 10032, USA
Keywords: Hemofiltration; Vasopressin; Pediatric
Abstract Hypothesis: As vasopressin is a small peptide, its sieving coefficient (SC) and clearance (CL) during continuous renal replacement therapy may be intermediate to those for urea and β2 microglobulin (commonly used markers for small– and middle–molecular weight solutes, respectively). Methods: A prospective, minimal-risk study was undertaken of the SC and CL of vasopressin in critically ill children on the first day of continuous renal replacement therapy using AN69 membrane filters and prefilter replacement fluid. All prefilter plasma (vasopressin) samples were drawn from the arterial port after predilution. Results: Nine patients with fluid overload, renal failure, or both were recruited (median age, 14 years) during the first day of either continuous venovenous hemofiltration (n = 3) or hemodiafiltration (n = 6). Multiorgan dysfunction syndrome was present in 8 patients, and 3 were in shock (2 were receiving a vasopressin infusion). Median prefilter plasma (vasopressin) was 1.7 pg/mL, although data points were skewed: 5 patients had a low prefilter plasma (vasopressin) (b2 pg/mL), and 4 patients (including 2 receiving a continuous vasopressin infusion) had a prefilter plasma (vasopressin) between 4.2 and 56.4 pg/mL. All those with low prefilter plasma (vasopressin) had an effluent (vasopressin) less than the detection limit (0.6 pg/mL). The median SC was 1 in the 4 patients with a measurable effluent (vasopressin), and their median filter CL was 48 mL/min or 39 mL/(min 1.73 m2). Conclusions: The SC and CL of vasopressin by continuous venovenous hemofiltration or hemodiafiltration in these critically ill children were similar to values for urea. © 2010 Elsevier Inc. All rights reserved.
Solute clearance (CL) during continuous renal replacement therapy (CRRT) is dependent in part on molecular weight: small–molecular weight solutes like urea (60 d) have a high sieving coefficient (SC) and are more easily cleared than middle–molecular weight solutes like β2 microglobulin (12 kd). Of note, convective CL for both small– and middle– molecular weight solutes increases with increasing ultrafilE-mail address: [email protected]. 0883-9441/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2010.03.005
tration rate (Quf), whereas the substitution of a diffusive modality (dialysis) increases CL of small–molecular weight solutes but decreases CL of middle–molecular weight solutes [1,2]. Substances larger than β2 microglobulin have lower SC and CL; and adsorption by the hemofilter may further limit convective CL, particularly for some very dilute proteins [3]. Substances with a molecular weight at or greater than the pore size of the hemofilter membrane are not cleared by convection or diffusion.
592 The molecular weight of vasopressin is approximately 1 kd, intermediate to urea and β2 microglobulin; and its CL during continuous arteriovenous hemofiltration in adults without critical illness was high in one study (N100 mL/min) [4]. However, there are currently no data regarding vasopressin CL during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF), including in particular during critical illness at any age. This study was designed to assess both the SC and CL of vasopressin early during CRRT of critically ill children, including children receiving an infusion of vasopressin. It was hypothesized that the SC and CL of vasopressin would be intermediate to values for urea and β2 microglobulin.
1. Materials and methods A prospective study at the Morgan Stanley Children's Hospital–Columbia University College of Physicians and Surgeons was approved by the Institutional Review Board, and recruitment occurred from May 2006 through September 2008. There were no financial or personal relationships with other people or organizations that could inappropriately influence or bias this work.
1.1. Eligible patients Children older than 1 year and weighing more than 10 kg who were treated with CRRT were eligible for recruitment to this study during the first day of CRRT following informed verbal consent. The requirement to obtain written documentation of informed consent was waived, as the study was judged to involve minimal risk, based on a total blood requirement for the study of less than 1% of estimated blood volume for each patient.
1.2. Procedures Demographic, clinical, laboratory, and treatment data were obtained by review of the medical record. Organ dysfunction was determined for each patient at the initiation of CRRT, according to criteria for multiorgan dysfunction syndrome (MODS) [5]. The diagnosis of shock was based on the clinical diagnosis of shock by the patient's attending pediatric intensivist. The Gambro PRISMA device (Cobe-Gambro Healthcare, Lakewood, CO) with an AN69 polyacrylonitrile filter in a Gambro M100 filter set (surface area, 0.9 m2; cutoff value of 35-40 kd [6]; Cobe-Gambro Healthcare) was used in all patients. The CRRT mode was determined by the attending physician in the pediatric intensive care unit. All replacement fluid was infused prefilter. Patients with severe coagulopathy did not receive anticoagulation; heparin was used in the remaining patients with a goal of a circuit partial thrombo-
J.S. Baird plastin time of 60 to 80 seconds. All blood draws were taken from the hemofilter circuit: 5 mL of blood (or effluent) was drawn for each specimen in an EDTA tube. Prefilter blood was drawn from the arterial port after predilution; postfilter blood and effluent specimens were drawn from the appropriate ports. To maintain the minimal-risk status of this study and yet obtain the maximum amount of data, the SC (ie, a single prefilter blood draw of 5 mL with a concurrent effluent specimen) was assessed in children weighing 10 to 25 kg during the first day of CRRT, whereas the SC and a postfilter specimen (ie, a single blood draw of 10 mL) were assessed in children weighing 25 to 40 kg. For children weighing more than 40 kg, these specimens were drawn on day 1 and again on day 2 of CRRT. Blood or effluent was immediately centrifuged and separated; and plasma or effluent was frozen at −80°C. The Irving Center for Clinical Research at Columbia University College of Physicians and Surgeons performed all vasopressin assays using an ultrasensitive radioimmunoassay (ALPCO Diagnostics, Salem, NH).
1.3. Calculations The following formulas were used for calculations: – – – –
Quf = replacement rate + net fluid removal rate Effluent rate = Quf + dialysate rate SC = effluent (vasopressin)/prefilter (vasopressin) Filter CL = SC × effluent rate
When using CVVH, filter CL is convective CL (and effluent rate = Quf), whereas during CVVHDF, filter CL is a combination of convective and diffusive CL. To minimize blood draws and maintain minimal-risk status for this study, blood for plasma (vasopressin) levels from the arterial port before predilution were not drawn.
1.4. Statistical analysis Data are presented as medians (mean; range). Statistical tests (Spearman rank correlation) were 2-sided with significance set at P b .05. All statistical analyses were performed using InStat version 3.06 (GraphPad Software Inc, San Diego, CA).
2. Results Nine patients were recruited: age, diagnoses, the incidence of MODS and shock, and indications as well as CRRT mode are presented in Table 1. Two patients treated with a vasopressin infusion initiated before CRRT received the same vasopressin dose throughout the study (0.0003 and 0.0008 U/kg/min). Vascular access for CRRT was obtained using dual-lumen catheters (size: 7F, 9F, or 11F; MedComp
Sieving coefficient and clearance of vasopressin during CRRT Table 1
Characteristics of study population (N = 9)
Median age, y (range) Diagnosis Oncologic disease (%) Systemic lupus erythematosus (%) Renal failure (%) Other disease (%) MODS (%) Shock (%) Vasopressin infusion (%) a Catecholamine infusion (%) a CRRT indications Renal failure (%) Fluid overload (%) Renal failure + fluid overload (%) CVVH:CVVHDF Survivors (%) Deaths during the study period
14 (1-19) 3 (33) 2 (22) 2 (22) 2 (22) 8 (89) 3 (33) 2 (22) 2 (22) 1 (10) 2 (20) 6 (67) 3:6 5 (56) 0
593 patient. This last patient developed unremitting septic shock on the second day of hemofiltration coincident with the decline in prefilter plasma (vasopressin) and intermittent difficulty maintaining hemofiltration flow; she died 2 days later. Data for SC and CL on the second day of CRRT were therefore unavailable in this cohort. Serum (sodium) did not correlate with prefilter plasma (vasopressin) (P = .16 by Spearman rank correlation). Median serum (sodium) was 145 (range, 134-156) mmol/L. Four patients died during their hospitalization (2 with stem cell transplant for oncologic disease, 1 with systemic lupus erythematosus, 1 with short gut syndrome and liver failure), none during the study period.
3. Discussion
a
One patient in shock was treated both with vasopressin and a catecholamine infusion.
Duo-Flow, Harleysville, PA) via the femoral (n = 8) or subclavian (n = 1) veins, and catheter ports were used in the intended configuration only (ie, the arterial or red port was used for hemofilter circuit inflow, whereas the venous or blue port was used for hemofilter circuit outflow). The replacement fluid was a bicarbonate-saline mixture (35 mEq Na bicarbonate and 104 mEq NaCl/L), whereas the dialysate fluid was Prismasate BK 0/3.5 (Gambro). Median effluent rate was 34 (mean, 30; range, 2-68) mL/min. Median prefilter plasma (vasopressin) was 1.7 pg/mL in all 9 patients on the first day of CRRT, although data points were skewed: 5 patients had a low prefilter plasma (vasopressin) (b2 pg/mL), and 4 patients (including both patients receiving a continuous vasopressin infusion) had a prefilter plasma (vasopressin) between 4.2 and 56.4 pg/mL. There did not appear to be an association with CRRT mode (CVVH vs CVVHDF) and prefilter plasma (vasopressin): 3 patients treated with CVVHDF had low levels, and 3 did not. All those with low prefilter plasma (vasopressin) had an effluent (vasopressin) less than the detection limit (0.6 pg/mL). Median values for postfilter plasma (in 7 of 9 patients) and effluent (in all 9 patients) (vasopressin) were 1.5 (0.6-42) and b0.6 (b0.6-51) pg/mL. The median SC was 1 (mean, 1.1; range, 0.9-1.7) in the 4 patients with a measurable effluent (vasopressin), and their median filter CL was 48 (mean, 42; range, 2-71) mL/min at a median effluent rate of 38 (mean, 36; range, 2-68) mL/min; corrected for body surface area, this corresponded to an effluent rate of 39 (mean, 47; range, 7-102) mL/min/1.73 m2. Prefilter plasma and effluent (vasopressin) were also assayed on day 2 of CRRT in 4 of 9 patients: prefilter plasma (vasopressin) was 1.4, 0.6, 1.7, and 37 pg/mL on day 1 vs 1.5, 0.6, 0.8, and 12 pg/mL on day 2, respectively; effluent (vasopressin) remained less than 0.6 pg/mL for the first 3 patients on both days and fell from 38 to 7 pg/mL in the last
The SC for urea using an AN69 membrane hemofilter and prefilter replacement is near 1 [2]; as a result, its CL, either via convection [2] (CVVH) or via a combination of convection and diffusion [1] (CVVHDF), approximates the effluent rate, whereas β2 microglobulin has an SC less than 0.6 and a proportionally lower CL under similar conditions [1,2]. The results of this study suggest that, in this setting, vasopressin is filtered and cleared like urea. As the vasopressin levels in this population of critically ill children were skewed, a larger study is needed to verify if vasopressin is routinely cleared like small–molecular weight substances. Further investigation of vasopressin's SC at various effluent rates will be helpful to determine if the SC remains constant: Brunet et al [1] found a variable SC for β2 microglobulin that increased in a nonlinear fashion with increasing Quf. If the filter consistently sieves all of the vasopressin presented to it (SC = 1), a higher Quf would lead to increasing CL of vasopressin, whereas if sieving is dependent in part on Quf, CL would be much less effective at a lower Quf. Potential limitations to this study also include the accuracy of the vasopressin assay (particularly at the lower detection limit), possible hemofiltration access recirculation, and the lack of plasma (vasopressin) values from the arterial port before predilution. In response, values for vasopressin in several patients assayed on the first and second day of hemofiltration appeared similar (including those patients with low levels); the median postfilter vasopressin level was slightly less than the median prefilter vasopressin level; all specimens were processed immediately (thus limiting possible degradation); and prefilter plasma (vasopressin) was higher in children receiving a vasopressin infusion, as one might predict. Assay accuracy therefore appeared acceptable. Access recirculation may, in theory, affect CL during CRRT, although available data suggest that this is minimal when CRRT catheters are used—as in this study— as per recommendations [7]. Vasopressin CL assessed in this study reflects CL across the hemofilter and not CL delivered to the patient: predilution is responsible for a decrease in CL
594 delivered to the patient, as CL across the filter is always greater than total CL delivered to the patient. Measurement of plasma (vasopressin) before predilution would allow the magnitude of the difference between filter and patient CL of vasopressin to be quantified; however, filter CL of urea is similar to filter CL of vasopressin as noted above, suggesting that vasopressin is cleared by the hemofilter much like urea during CRRT. Vasopressin CL by CRRT deserves further investigation, particularly as CL during CVVH of another small peptide with hemodynamic consequences—brain natriuretic peptide —has recently been shown to lead to a significant decline in this peptide in infants [8].
References
J.S. Baird
[2]
[3]
[4]
[5]
[6] [7] [8]
[1] Brunet S, Leblanc M, Geadah D, Parent D, Courteau S, Cardinal J. Diffusive and convective solute clearances during continuous renal
replacement therapy at various dialysate and ultrafiltration flow rates. Am J Kidney Dis 1999;34:486-92. Troyanov S, Cardinal J, Geadah D, Parent D, Courteau S, Caron S, et al. Solute clearances during continuous venovenous haemofiltration at various ultrafiltration flow rates using Multiflow-100 and HF1000 filters. Nephrol Dial Transplant 2003;18:961-6. De Vriese AS, Colardyn FA, Philippe JJ, Vanholder RC, De Sutter JH, Lameire NH. Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol 1999;10:846-53. Pruszczynski W, Viron B, Mignon F, Ardaillou R. Massive plasma arginine vasopressin (AVP) removal during hemofiltration stimulates AVP secretion in humans. J Clin Endocrinol Metab 1987;64:383-6. Proulx F, Gauthier M, Nadeau D, Lacroix J, Farrell CA. Timing and predictors of death in pediatric patients with multiple organ system failure. Crit Care Med 1994;22:1025-31. Chanard J, Toupance O, Gillery P, Lavaud S. Evaluation of protein loss during hemofiltration. Kidney Int Suppl 1988;24:S114-6. Schetz M. Vascular access for HD and CRRT. Contrib Nephrol 2007;156:275-86. Ricci Z, Garisto C, Morelli S, Di Chiara L, Ronco C, Picardo S. Brain natriuretic peptide is removed by continuous veno-venous hemofiltration in pediatric patients. Interact Cardiovasc Thorac Surg 2009;9:33-6.