925CHAPTER 75 Pediatric Renal Replacement Therapy in the Intensive Care Unit When solute clearance or ultrafiltration is suboptimal with conventional PD or the patient cannot tolerate high fill volume[.]
CHAPTER 75 Pediatric Renal Replacement Therapy in the Intensive Care Unit When solute clearance or ultrafiltration is suboptimal with conventional PD or the patient cannot tolerate high fill volumes, one may consider the technique of continuous-flow peritoneal dialysis (CFPD) CFPD requires two dialysis catheters placed in the peritoneum, one for inflow and the other for outflow of peritoneal fluid.35 There is no dwell time per se as the peritoneal fluid is in constant transit through the peritoneum CFPD can result in a fivefold increase in clearance and a ninefold increase in ultrafiltration.36 Experience with CFPD is limited; thus, it cannot be considered a standard technique in pediatrics at this time, although it may hold promise in the future Disadvantages and Complications The PD technique requires placement of a peritoneal catheter and a sufficiently maintained intraabdominal status to permit infusion of dialysate with successful diffusion and ultrafiltration Patients who have undergone an abdominal operation or have had abdominal complications may be poor candidates for PD Invasion of the peritoneal space puts the patient at risk for peritonitis, a potentially serious complication The importance of sterile technique when performing PD cannot be overemphasized Appropriate technique limits, but does not eliminate, the risk of infectious complications, which could be fatal in a critically ill patient One must always consider peritonitis in a patient undergoing PD who has a fever or cloudy effluent Dialysate should be analyzed for cell count, Gram stain, and bacterial culture if infection is suspected Empirical or specific antibiotics can be placed in the dialysate to treat peritonitis via the intraperitoneal route.37 Dialysate can fail to fill or drain through the PD catheter because of a number of potential problems, including kinking of the catheter, fibrin plugs, omental obstruction, and catheter malposition Percutaneously inserted temporary dialysis catheters are more prone to malfunction than are surgically placed catheters.38 Abdominal radiographic images can confirm appropriate positioning and permit checks for kinks in the catheter Some success has been reported with thrombolytic agents to treat fibrin plugging.39–41 If simple maneuvers not correct the malfunction, the catheter may need to be revised or replaced Perforation of abdominal or pelvic structures can occur, either at the time of initial catheter placement or later.38 Although this event is relatively uncommon, significant morbidity can result PD is a suboptimal choice for patients who require rapid correction of metabolic abnormalities, immediate removal of circulating toxins, or rapid ultrafiltration for acute complications of fluid overload For these indications, hemodialysis is preferred Effectiveness of PD may be suboptimal in settings of low cardiac output with splanchnic circulation compromise However, this does not preclude the use of PD in selected cases, such as for infants following surgery for congenital heart disease.28–30 Fluid leakage is seen most often with dwell volumes that are too large, especially in the period immediately after catheter placement.42 Lower fill volumes should be used Fluid leakage into the thorax can compromise respiration External fluid leakage around the catheter increases the risk of infection Intensive Care Unit Issues Patients undergoing PD can lose protein into the dialysate Nutritional support must provide sufficient protein to compensate for this loss High dextrose concentrations in the dialysate can 925 cause hyperglycemia; administration of insulin may be necessary Indwelling dialysis fluid causes increased intraabdominal pressure that can complicate care of the critically ill patient Diaphragmatic excursion may be limited and venous return can be reduced Stomach compression can lead to gastroesophageal reflux Although patients undergoing long-term PD who receive fewer daily exchanges usually require maximal fill volumes to achieve adequate dialysis, patients undergoing short-term PD may better using submaximal fill volumes with more frequent exchanges provided around the clock Intermittent Hemodialysis Intermittent hemodialysis (IHD) is a well-established technique for pediatric patients.43 IHD offers the advantage of efficient fluid and toxin removal for prompt metabolic and volume correction High efficiency requires rapid blood and dialysate flow Factors that prevent achievement of high blood flow include systemic hypotension and a narrow vascular access IHD for infants and small children can be technically demanding due to access difficulties and relatively large extracorporeal blood volume IHD may be the preferred modality for some critically ill pediatric patients who require rapid removal of a specific toxin Successful treatment in this setting requires experienced personnel Physiology The dialyzer used in IHD is an artificial semipermeable membrane The modern hollow-fiber dialyzer consists of a plastic cartridge traversed by several thousand thin capillary fibers, each with microscopic fenestrations that permit the passage of water and other small molecules Dialyzers vary in surface area, permeability, priming volume, and membrane composition; numerous dialyzers are available commercially Choosing different dialyzer characteristics permits adjustment of the dialysis prescription to the clinical situation While blood flows through the hollow fibers of the dialyzer, dialysate flows through the cartridge in the space surrounding the fibers Particles move by diffusion from the blood across the semipermeable membrane into the dialysate Use of high-flow dialysate with maximal blood flow through the dialyzer permits IHD to remove particles more efficiently than any other RRT Increasing blood flow, dialysate flow, or dialyzer size will increase the rate of diffusion Because diffusion favors the movement of small particles over large particles, large molecules or small molecules bound to larger molecules (such as albumin) will not dialyze well In addition, intracellular particles will move into the vascular compartment based on individual cell membrane transport characteristics, which may limit the rate at which dialysis can remove particles that not reside within the vascular compartment Ultrafiltration on hemodialysis occurs because of hydrostatic pressure across the membrane that forces water out of the blood Dissolved particles will travel with the water, leaving by convection Dialysis staff can control the rate of ultrafiltration with precision and can achieve high rates of ultrafiltration Analogous to the process of diffusion, ultrafiltration during IHD removes fluid only from the vascular compartment Extravascular or third-space fluid must move into the vascular compartment for removal by ultrafiltration When the rate of movement from the extravascular space is slower than the rate of ultrafiltration, intravascular depletion can occur even though total 926 S E C T I O N V I I Pediatric Critical Care: Renal BP Extravascular compartment Vascular compartment • Fig 75.3 Two-compartment model of ultrafiltration The rate of water removal from the vascular compartment by ultrafiltration (large arrows) exceeds the rate of refilling from the extravascular compartment (smaller arrows) This process leads to relative vascular volume depletion and hypotension BP, Blood pressure body water remains elevated (Fig 75.3) This two-compartment model represents a potential limitation of rapid ultrafiltration during IHD, especially in the critically ill patient Indications Due to its high efficiency, hemodialysis is the best modality for rapid particle removal IHD is indicated for the treatment of toxic ingestions, many serious drug overdoses, and metabolic derangements that lead to the overproduction of endogenous toxins such as ammonia.44–47 The IHD system can perform ultrafiltration more rapidly than any other renal replacement modality Consequently, it is often the best choice for the treatment of critical volume overload but may be limited by the patient’s ability to tolerate rapid fluid removal Technology to guide ultrafiltration by the noninvasive monitoring of hematocrit changes during IHD may prevent or mitigate hypotension associated with ultrafiltration.48 Profound metabolic imbalance, such as that seen with critical hyperkalemia, corrects most quickly with IHD Patients with oncologic problems such as tumor lysis syndrome may require IHD to rapidly correct the multiple metabolic abnormalities and to aid clearance of uric acid, which can cause AKI.49,50 Technique Vascular access is the first step for successful hemodialysis Doublelumen catheters for hemodialysis come in a variety of sizes Occasionally, two single-lumen catheters at separate sites are needed for small infants, although data suggest that these catheters not perform as well.51,52 Catheters can be placed in jugular, femoral, or subclavian positions The most desirable site for a double-lumen hemodialysis catheter is the right internal jugular vein It provides access to a high-flow area in the superior vena cava/right atrium, permits a straight venous path from insertion site to target location, can be readily accessed for insertion of either tunneled or nontunneled catheters depending on the indication, allows ambulation and reduces discomfort for the patient as compared with the femoral site, and is less susceptible to complicating venous stenosis that will limit future permanent dialysis vascular access creation (e.g., arteriovenous [AV] fistula) By contrast, subclavian access is associated with increased risk of stenosis that would result in loss of potential sites for AV fistula formation in the ipsilateral arm In neonates, umbilical catheters have been used if other access has failed However, umbilical catheters are often not successful due to poor flow dynamics and are not recommended Most patients receiving IHD will require anticoagulation therapy to prevent clotting within the dialysis circuit Any anticoagulant can be used, with goal activated clotting time to be 1.5 to times normal Unfractionated heparin is the most common anticoagulant for IHD Some may be able to undergo successful dialysis with little or no heparin because of coagulopathy related to systemic disease If regional anticoagulation (anticoagulation of the dialysis circuit without systemic effects) is preferred, dialysate containing citrate is available.53 The citrate in the dialysate will bind calcium locally at the dialyzer membrane, limiting clotting within the dialyzer Monitoring of ionized calcium is not required as the concentration of citrate is low; thus, the patient is not at risk for hypocalcemia Clinical experience thus far shows citratecontaining dialysate to be effective as an anticoagulant but some centers find that low-dose systemic heparinization is required.54 The blood pump rate depends on the patient’s clinical status and the quality of the vascular access In smaller patients with smaller catheters, blood pump speeds may be less than 100 mL/ min; in infants, speeds may run as low as 25 to 50 mL/min Larger patients can tolerate faster blood pump speeds Higher blood flow rates permit greater IHD efficiency The chosen dialyzer should provide sufficient clearance to achieve the goals of the dialysis session Smaller patients receive dialysis with smaller dialyzers to limit extracorporeal blood volume and reduce the risk of dialyzer clotting with slower blood flow rates Small patients or those with unstable blood pressure may require priming of the IHD circuit with saline solution, albumin, or reconstituted whole blood Dialysis machines with precise volumetric ultrafiltration control permit accurate and safe IHD in neonates and infants, for whom small inaccuracies in ultrafiltration volumes could potentially lead to severe fluid imbalances One may make some adjustments to the electrolyte concentrations in dialysis fluid depending on the clinical situation The length of the IHD session will vary depending on the clinical situation and goals of the therapy Mathematical models permit estimation of dialytic clearance and help to structure session length The rate at which the patient can tolerate ultrafiltration is often the limiting factor in IHD for critically ill patients; one may need to extend the session length to achieve ultrafiltration goals without significant hypotension Disadvantages and Complications The principal disadvantage of IHD is the requirement for vascular access Acceptable access can be difficult to achieve in critically ill children Complications related to the access can include infection, bleeding, and thrombosis IHD’s benefit of high efficiency with rapid fluid and particle removal can lead to difficulties in the ICU setting Critically ill patients may not tolerate the rapid ultrafiltration and metabolic shifts of IHD Smaller patients or those with unstable blood pressure may require priming of the extracorporeal circuit to limit hemodynamic stress at dialysis initiation For infants in whom the extracorporeal CHAPTER 75 Pediatric Renal Replacement Therapy in the Intensive Care Unit volume is relatively much larger, priming may require a blood/ albumin mix, which exposes the patient to blood products Most IHD sessions require systemic anticoagulation with heparin, which can be difficult to manage in a critically ill child Heparin exposure can complicate bleeding and cause heparininduced thrombocytopenia With careful monitoring of clotting times and circuit performance during the session, it is possible to perform IHD without anticoagulation Regional anticoagulation is also available with dialysate containing citrate Intensive Care Unit Issues Patients receiving IHD as ongoing RRT in the ICU require special attention to fluid and electrolyte balance One should limit potassium and phosphorus delivery and may need to limit total daily fluids because ultrafiltration occurs only intermittently Administer blood during dialysis to remove excess potassium Medication doses and schedule may require adjustment because of poor excretion with renal failure and subsequent rapid removal with dialysis Continuous Renal Replacement Therapy CRRT is a generic term applied to several techniques of extracorporeal renal support Similar to IHD in the use of a blood pump and hemofilter, the various subcategories of CRRT differ in their reliance on diffusion, convection, or a combination of the two for molecular clearance CRRT has become more popular as a method of renal support for pediatric patients.1,52 Technologic improvements in catheters, blood pumps, and ultrafiltration control mechanisms permit the application of CRRT to even the smallest infants.55,56 Compared with IHD, data suggest that continuous modalities of RRT may increase the likelihood of recovery of renal function in critically ill survivors of AKI.20,21 Physiology The CRRT hemofilter is similar to that used for IHD CRRT membranes traditionally have been more porous to permit greater removal of water Numerous hemofilters are available commercially CRRT may employ both convection and diffusion Dialysate allows diffusion, which favors the movement of smaller molecules High rates of ultrafiltration will remove both small and larger particles by convection, up to the limits of the membrane With high ultrafiltration rates to achieve better convective clearance, the patient may need to receive replacement of volume and electrolytes to compensate for that lost in ultrafiltrate Because of slower flow rates, clearance with CRRT may be lower than IHD Continuous therapies make up for this lower efficiency through the extended treatment time Compared with a 3- or 4-hour IHD session, CRRT running 24 hours a day can achieve equivalent daily clearance with less metabolic variation Newer CRRT devices can run at flow rates approaching those seen in IHD, greatly increasing the potential for rapid molecular clearance Nomenclature for the subcategories of CRRT derives from the vascular access and primary method of particle clearance (convection, diffusion, or both) Because most CRRT in pediatric patients uses a pump-assisted venovenous method, the most commonly used terms are continuous venovenous hemofiltration 927 (CVVH), which uses high convective clearance requiring replacement fluids; continuous venovenous hemodialysis (CVVHD), which uses dialysis fluid for diffusion but minimal additional convection; and continuous venovenous hemodiafiltration (CVVHDF), which uses both dialysis fluid and replacement fluids for combined diffusion and high-grade convection Indications CRRT is particularly well suited to the treatment of volume overload in critically ill patients Whereas IHD will attempt to reach an ultrafiltration goal within a relatively short therapeutic session, CRRT allows continuous ultrafiltration that can help maintain cardiovascular stability CRRT is useful to maintain metabolic balance through ongoing removal of unwanted particles Although it is less efficient than IHD, CRRT’s continuous nature can avoid daily fluctuations inherent in the use of an intermittent modality In addition, CRRT can maintain metabolic balance after rapid correction with IHD.57 For patients with diminished renal function and decreased urinary output, CRRT allows administration of the daily load of fluids and clearance required to deliver medication, nutrition, and blood products With this modality, the patient can be maintained in a more stable balance compared with IHD, in which the patient has progressive volume overload between IHD sessions and then must achieve the ultrafiltration goal in a brief treatment period Technique As in IHD, successful CRRT requires adequate vascular access Given the relatively large extracorporeal volume, smaller patients may require priming of the CRRT circuit with blood/albumin mix Larger, more stable patients may initiate CRRT with saline prime Several CRRT systems are available at this time The latest generation of CRRT machines permits much greater accuracy for blood pump speed, fluid delivery, and ultrafiltration control Anticoagulation Adequate anticoagulation is essential for successful CRRT Systemic heparinization has been the traditional form of anticoagulation used in CRRT This proven method functions well Disadvantages include systemic anticoagulation with risk of bleeding, risk of heparin-induced thrombocytopenia, and the need for frequent monitoring and adjustment of the heparin dose Regional citrate anticoagulation has become popular for CRRT in both adult and pediatric patients Citrate, introduced into the CRRT circuit, chelates calcium, which is a required cofactor in both the intrinsic and extrinsic arms of the clotting cascade Calcium is infused back into the patient through a central access to prevent systemic hypocalcemia Citrate is metabolized to bicarbonate, acting as a source of base Several protocols have been developed for regional citrate anticoagulation in CRRT.58–61 They are stable and require less monitoring than heparin-based anticoagulation Disadvantages include the potential for acid– base imbalance, the risk of hypercalcemia or hypocalcemia, citrate excess due to poor metabolism or diminished clearance, and the need for additional central access for high rates of calcium delivery Many critically ill patients have disorders of coagulation as a part of their multiple-organ system injury and can undergo 928 S E C T I O N V I I Pediatric Critical Care: Renal CRRT without exogenous anticoagulation Increased clotting of the CRRT circuit in such patients may be a sign of improving clinical status A study of pediatric CRRT suggested that circuits that are run without anticoagulation have a significantly shorter life span; thus, it may be appropriate to consider the use of anticoagulation even in the coagulopathic patient to ensure continued delivery of the therapy.62 Patient and vascular access size can limit blood pump rate The current generation of CRRT machines can run at lower blood pump speeds with greater accuracy than did earlier systems Many brands of hemofilters are available for CRRT Larger surface areas will permit more rapid ultrafiltration and clearance by convection Of particular interest in the pediatric patient are reports of profound hypotensive events related to the use of a type of polyacrylonitrile hemofilter known as the AN-69 membrane.63 This reaction, seen when the patient’s blood comes in contact with the hemofilter, is thought to be related to the release of bradykinin in response to the low pH of blood used to prime the CRRT circuit Smaller patients and those with metabolic acidosis seem to be at greatest risk One may attempt adjustment of pH within the circuit to limit this reaction63–65 or choose to avoid use of the AN-69 membrane Dialysate and Infused Fluids Nearly all of the current CRRT machines use premade, fully compounded dialysate or hemofiltration fluid rather than generating dialysis fluid online from concentrates (as in IHD) Several manufacturers offer solutions for CRRT; the products come in a variety of electrolyte concentrations to suit differing clinical needs It has been suggested that the use of commercial CRRT solutions, rather than those made by a local pharmacy, can reduce the likelihood of errors related to solution preparation.66 Replacement fluids are infused to the CRRT system either before the hemofilter (“prefilter” or “predilution”) or after (“postfilter” or “postdilution”) Prefilter delivery reduces convective clearance at a given ultrafiltration rate due to dilution of the blood; increasing the ultrafiltration rate can overcome this issue Prefilter replacement also may permit higher ultrafiltration rates because it limits hemoconcentration within the hemofilter, reducing the chances of filter clotting This may be less of a concern with citrate anticoagulation, which is very effective at preserving filter life Some CRRT machines will permit either prefilter or postfilter delivery of replacement fluids while others have a fixed location for replacement fluids Clearance In most prescriptions, the limiting factor in CRRT clearance is the solution flow rate; greater rates of clearance often can be achieved with an increase in the rate of dialysate or replacement fluid Newer CRRT machines are capable of higher solution rates than in the past Slower blood pump speeds can also potentially limit clearances; some newer devices are capable of higher blood pump speeds Controversy exists in adult patients regarding appropriate goals for clearance An influential single-center study suggested better outcomes with higher rates of clearance,67 but this finding has not been reproduced in subsequent multicenter trials.68,69 This question has not been fully studied in children Slow, steady ultrafiltration to gradually achieve fluid balance and then maintain it is the hallmark of CRRT Slow ultrafiltration can permit movement of extravascular fluid into the vascular space at a rate roughly equal to the ultrafiltration rate, which allows greater mobilization of fluid while limiting the risk of acute intravascular volume depletion and hypotension Clinical status of the patient and fluid balance goals guide ultrafiltration rates; frequent reevaluation is necessary Disadvantages and Complications Like IHD, CRRT requires vascular access, which can be difficult to obtain in infants and small children Data suggest that Fr single-lumen catheters should not be used for CRRT because they are associated with significantly shorter functional CRRT circuit survival.51 Continuous extracorporeal perfusion and anticoagulation carry risks of bleeding and infection Some patients experience blood pressure instability despite the slow method of ultrafiltration Continuous exposure to heparin can lead to heparin-induced thrombocytopenia Patients receiving citrate anticoagulation are at risk for acid–base disturbance or hypocalcemia Citrate excess can cause low patient ionized calcium with normal or high total calcium levels, the so-called calcium gap or citrate lock,59,70 which occurs when excess citrate binds free calcium in the patient Under these circumstances, one may reduce citrate delivery or increase CRRT clearance Intensive Care Unit Issues Continuous clearance on CRRT, particularly with convective modalities, can cause profound electrolyte deficiencies requiring replacement Similarly, nitrogen losses on CRRT can be high.71 Patients require increased nutritional support during CRRT therapy with careful consideration of the nutritional prescription.72 Medication dosages often require adjustment because of CRRT clearance Coordination between the ICU staff and nephrology staff is essential to establish appropriate goals for fluid removal and metabolic control Extended Dialysis One may extend IHD sessions to provide therapy that approaches CRRT Variously referred to as slow low-efficiency dialysis or slow extended daily dialysis, such techniques can provide improved molecular clearance with better tolerance of ultrafiltration when compared with conventional schedules for IHD Sessions may run to hours or more on a daily basis.73 Some institutions may prefer extended dialysis methods because they obviate the need to purchase and maintain separate dedicated CRRT equipment, using instead standard IHD machines that have been adapted for longer session length In addition, disposable materials are usually less expensive than for CRRT, potentially leading to cost savings Online generation of dialysate, as for standard IHD, greatly simplifies solution delivery compared with premixed bags that must be frequently exchanged for CRRT However, most online dialysate is not sterile, raising a theoretic risk for the critically ill patient Newer devices capable of extended therapies can be adapted to provide ultrapure dialysis fluid, which may mitigate this potential concern Outcomes of Renal Replacement in Critically Ill Children Outcome data comparing modalities for pediatric renal replacement are sparse Most studies are from single centers and are limited by small numbers of subjects CHAPTER 75 Pediatric Renal Replacement Therapy in the Intensive Care Unit Studies in pediatric RRT have centered on CRRT Findings from five studies, comprising an aggregate of more than 400 patients, demonstrate an association of higher mortality for patients with more severe levels of volume overload.8–11,74 A multicenter observational registry has provided insight on outcomes in pediatric CRRT.56 Overall survival on CRRT in this cohort of more than 300 critically ill children was 58% This percentage is superior to previously reported outcomes and likely represents improvement in CRRT techniques as well as overall critical care for the pediatric patient Outcomes in the subpopulations of children with multisystem organ dysfunction and stem cell transplant who required CRRT also were noted to be improved compared with historical reports.8,75 Because these studies did not compare CRRT to other interventions, no specific evidence-based comments can be made regarding choice of modality in the modern era; this decision is largely based on experience and opinion Advances in Pediatric Renal Replacement Therapies Pediatric RRT traditionally has come from adaptation of adult technologies to the pediatric patient Advancement in technology has resulted in smaller filter size, permitting lower blood flow rate and reduced extracorporeal blood volume Despite these advancements, RRT for smaller patients remains a challenge; some consider manual PD as the only option in patients who weigh less than kg Newer CRRT devices, designed specifically for infants, offer the hope of providing RRTs safely to neonates and small children.76,77 Summary Pediatric patients who require RRT represent a special challenge Multiple modalities are available; the best choice may be dictated by the clinical situation and local expertise Careful attention to fluid and electrolyte balance, appropriate nutritional support, and close interaction between critical care and nephrology personnel will yield the best outcomes 929 Key References Bellomo R, Cass A, Cole L, et al Intensity of continuous renalreplacement therapy in critically ill patients N Engl J Med 2009; 361(17):1627-1638 Brophy PD, Somers MJ, Baum MA, et al Multi-centre evaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT) Nephrol Dial Transplant 2005;20(7):1416-1421 Cullis B, Abdelraheem M, Abrahams G, et al Peritoneal dialysis for acute kidney injury Perit Dial Int 2014;34(5):494-517 Hackbarth R, Bunchman TE, Chua AN, et al The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry Int J Artif Organs 2007;30(12):1116-1121 Jetton JG, Boohaker LJ, Sethi SK, et al Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study Lancet Child Adolesc Health 2017;1(3): 184-194 Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, Investigators A Epidemiology of acute kidney injury in critically ill children and young adults N Engl J Med 2017;376(1):11-20 Palevsky PM, Zhang JH, O’Connor TZ, et al Intensity of renal support in critically ill patients with acute kidney injury N Engl J Med 2008;359(1):7-20 Ronco C, Bellomo R, Homel P, et al Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial Lancet 2000;356(9223): 26-30 Sutherland SM, Zappitelli M, Alexander SR, et al Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry Am J Kidney Dis 2010;55(2):316-325 Symons JM, Chua AN, Somers MJ, et al Demographic characteristics of pediatric continuous renal replacement therapy: a report of the prospective pediatric continuous renal replacement therapy registry Clin J Am Soc Nephrol 2007;2(4):732-738 The full reference list for this chapter is available at ExpertConsult.com ... overcome this issue Prefilter replacement also may permit higher ultrafiltration rates because it limits hemoconcentration within the hemofilter, reducing the chances of filter clotting This may... metabolic acidosis seem to be at greatest risk One may attempt adjustment of pH within the circuit to limit this reaction63–65 or choose to avoid use of the AN-69 membrane Dialysate and Infused... extravascular compartment (smaller arrows) This process leads to relative vascular volume depletion and hypotension BP, Blood pressure body water remains elevated (Fig 75.3) This two-compartment model represents