Practical aspects Induction of hypothermia will lead to the activation of counter-regulator y mechanisms to decrease heat loss, including an increase in sympathetic tone, vasoconstric tion of skin vessels and shivering. Shivering increases oxygen consumption by 40 \200\22310 0% and has been linked to increased risk of morbid cardiac events; however, these observati ons have been made in the post-operative setting, where hypo- thermic patients are awake an d have a high rate of metabo- lism, increased oxygen consumption, excess work of breathing, a high heart rate and a general stress-like response. These adverse events are linked to t he haemo- dynamic and respiratory responses rather than to shiver- ing per se, and the side effects are largely absent in controlled hypothermia where patients are sedated, venti- la ted and have low heart rates. However, shivering can gen- erate signi \201 cant amounts of heat and can signi \201 cantly decrease cooling rates; for this and other reasons it shou ld be aggressively treated (especially in the induction phase of cooling). Shivering respon ses decrease markedly when the temperature decreases below 33.5 \200\22334.0 C. Cardiovasc ular effects of cooling include bradycardia and a rise in blood pressure. Hypothermia \200 \231s effect on myocardial contractility is variable (depending on heart rate and \201 ll ing pressure); in most patients, myocardial contractility will increase, although mild dias tolic dysfunction may develop in some patients. Clinically signi \201 cant arrhythmias may occur, but only if core temperature decreases below 30 C. The most important long-term si de effect of hypothermia is an increased risk of infections (especially of the respira- tor y tract and/or wounds) and bedsores. The most important potential side effects of cooling a re: \200 Hypovolemia through hypothermia-induced cold diure- sis. If uncorrected this can cause hypotension. Hypothermia per se does not decrease blood pressure. Electrolyte disord ers (cooling causes urinary loss of K, Mg, P as well as intracellular shift; rapid re-warmi ng can cause hyperkalaemia). Hyperglycaemia (cooling can cause insulin resistance and decre ased insulin secretion). Shivering (can be controlled with magnesium, meperid- ine, quick-a cting opiates, propofol or benzodiazepines; additional therapeutic options include ketanser in, cloni- dine, tramadol, urapidil and doxapram). Skin injuries/bedsores (prolonged direct exposure of the skin to ice or ice-packs can cause burns; cooling causes vasoconstriction in the skin; and wound infections can develop more easily due to the immunosuppressive effe cts of hypothermia). Infections, especially airway and wound infections. De \201 nitions Induced hypothermia: an intentional reduction of a patient \200\231s core temperature below 36.0 C. Therapeutic hypothermia: controlled induced hypothermia, i.e. in duced hypothermia with potentially harmful effects such as shivering being controlled or su ppressed. Temperature range usually 32 \200\22335.9 C. A separate but closely related issu e is the use of controlled normothermia (therapeutic fever management). Several studies hav e demonstrated a link between fever (irrespec- tive of its cause) and a worsening of neurol ogical outcome in many types of neurological injury, including post-ischaemic injury follow ing cardiac arrest. This correlation persists after multivariate analysis, and observations from animal studies strongly suggest that the link is causal. Therefore, sympto- matic con trol of fever is becoming an increasingly accepted goal of therapy in patients with neurocr itical illness. Therapeutic normothermia: bringing down and maintaining core temperature wi thin a range of 36.0 \200\22337.5 C in a patient with fever, with the potentially deleteri ous effects such as shivering being controlled or suppressed. Temperature management in cri tically ill patients poses special challenges for attending physicians and nurses, as the i nduction strategy and proper management of side effects can have a substantial impact on ou tcome. The hypothermia treatment period can be divided into three distinct phases: Induction phase Aim: to achieve temperatures \211 34 C and then target tem- perature as q uickly as possible. In this phase, a small over- shoot ( \211 1 C) should be regarded as a cceptable provided core temperature remains >30 C. Maintenance phase Aim: to control core temperatures tightly within a narrow range, with no or minor \202 uctuations (maximum 0.2 \200\2230.5 C). Precautions \200 Treat infections early and aggressively; consider antibi- otic prophylaxis; perform frequen t cultures of blood and other sites. Re-warming phase Aim: slow and controlled rise in temperature, target rate 0.2 \200\2230.3 C/h, maximum acceptable rate 0.5 C/h. Reason: 61 CHAPTER 2.5 Therapeutic cooling Use appropriate sedation and analgesia (animal data sug- gest loss of protective effects if sedation is insuf \201 cient; sedation also facilitates cooling by preventing shivering a nd causing vasodilation). Adjust ventilator settings (cooling causes dO2 consump- tion and dCO2 production); adjust feeding rate (cooling decreases metabolism by 7 \200\22310% per C decrease below 37 C). Blood gas analysis and clotting parameters are affected by tempera ture. Most laboratories warm samples to 37 C before analysis. If blood gas results have no t been analyzed at the patient \200\231s true core temperature, values can be estimated wit h the following rule of thumb: for pO2, subtract 5mm Hg for every 1 C below 37 C; for pCO 2, subtract 2mm Hg for every 1 C below 37 C; for pH, add 0.012 points for every 1 C belo w 37 C. Adjust drug dosage (drug clearance, especially by the liver, may change; this incl udes clearance of sedatives, opiates and paralyzing agents. Precaution: use bolus doses dur ing induction phase, avoid high maintenance doses). Avoid core temperature \211 30 C (ris k of arrhythmias arises at temperatures \211 28 \200\22330 C). Hypothermia does not cause arrhythmias at temperatures \211 30 C. Avoid \200\230overtreating \200\231. Bradycardia , mild metabolic acido- sis and a slight rise in lactate levels, liver enzymes and amylase are normal consequences of hypothermia, and usually do not require treatment. Avoid long-te rm paralysis. Paralysis can mask inadequate sedation and seizures, and can have adverse con se- quences such as increased risk of critical illness polyneu- romyopathy. Treat shivering with one of the other agents listed above. Consider platelet administration before surgery or inva- sive procedures during cooling. General measures: provide good basic intensive ca re (many of the side effects of cooling can be prevented or controlled with proper intensiv e care treatment). by external cooling, the patient \200\231s normal counter-regulatory mechanisms will be act ivated. Indeed shivering may be more pronounced than in hypothermic patients, because where as at 33 C the shivering response is absent or signi \201 cantly blunted, at 36 \200\2233 7 C the counter-regulatory mechanisms are working at maximum capacity. Therefore, maintain ing controlled normothermia is often more dif \201 - cult than maintaining controlled hypo thermia, and extra efforts may be required to combat shivering. This is a prob- lem especia lly in non-ventilated patients, because the doses of sedatives required to control shiverin g may be so large that they can induce respiratory failure. Antipyretic drugs such as parac etamol (acetaminophen) or aspirin can be used as adjunctive treatment to lower tem- peratur e. A major advantage is that these drugs do not activate the shivering response. However, t heir ef \201 cacy (especially in non-infectious ( \200\230central \200\231) fever is relat ively low; the average temperature decrease in patients treated with high doses of paraceta mol or aspirin is 0.1 \200\2230.7. Conclusions There is an increasing awareness that temperature can sig- ni \201 cantly affe ct outcome in critically ill patients, especially those with neurological injuries. Therape utic temperature management is therefore likely to gain importance, not just in ICU patient s but (certainly in the case of controlled nor- mothermia) also in patients admitted to gen eral wards. Mild hypothermia appears to be well tolerated provided that the side effects ar e prevented or strictly controlled. Temperature control should be regarded as an important goal of therapy in critically ill patients, especially those with neurological injuries. Further reading Diringer MN, Reaven NL, Funk SE, et al. Elevated body temperature independe ntly contributes to increased length of stay in neurologic intensive care unit patients. Cr it Care Med 2004; 32: 1611 \200\2232. Nolan JP, Deakin CD, Soar J, et al. European Resuscitation Council. European Resuscitation Council guidelines for resuscitation 2005. Section 4. Adult advanced life support. Resuscit ation 2005; 67 Suppl 1: S39 \200\22386. Cooling methods A number of cooling devices have reached the market in recent years that en able reliable maintenance and slow and controlled re-warming. There are invasive systems (c ooling catheters for direct cooling of the blood) and non-invasive methods (water-circulati ng blankets and adhesive pads for surface cooling); 371;1955 \200\22369. Air-circulating co oling blankets are ineffective for cooling purposes, and should not be used for induction o f hypothermia. In the induction phase, rapid cooling rates can be achieved by combining an invasive or surface cooling device with rapid infusion of cold \202 uids (1500 \200\22330 00ml of 4 C saline or Ringers lactate using a pressure bag). Rapid cooling reduces the sev erity and duration of shivering, and decreases the risk of hypo- thermia-induced electrolyt e disorders. Polderman KH. Therapeutic hypothermia in the Intensive Care unit: problems, pitfalls and op portunities (review). Part 1: indications and evidence. Intensive Care Med 2004; 30: 556 \200\22375. Polderman KH: Application of therapeutic hypothermia in the intensive care unit. Opportunit ies and pitfalls of a promising treatment modality. Part 2: practical aspects and side effe cts. Intensive Care Med 2004; 30: 757-69. Polderman KH. Induced hypothermia and fever control for preven- tion and treatment of neuro logical injuries. Lancet 2008; in press. Polderman KH. Therapeutic hypothermia and controll ed normoth- ermia in the ICU: practical considerations, side effects and cool- ing methods. Crit Care Med 2008 (in press). Controlled normothermia Most of the side effects listed above do not occur during controlle d normothermia. However, shivering does occur because the hypothalamic temperature setpoint is elevated in patients with fever; thus, if core temperature is lowered This page intentionally left blank 63 Chapter 3 Renal therapy techniques Chapter contents Haemodialysis 64 Haemo(dia) \201 ltration 68 Peritoneal dialysis (PD) 70 64 A SHORT Haemodialysis A design that minimizes recirculation of treated blood should be used, e.g. shotgun. Tempor ary large bore arterial access is now rarely used. The \201 rst human haemodialysis was performed in 1943 by Willem Kolff in The Netherlands for the treatment of acute renal failure. Following this, haemodialysis was adopted for th e treatment of acute renal failure in the immediate post-war years and then for chronic ren al fail- ure from the 1960s. Currently haemodialysis is the most common form of replacement treatment for end-stage renal disease (ESRD). Haemodialysis is one method used for treatme nt of acute renal failure, and ESRD patients will develop critical illness. An understandin g of the principles of haemodialysis and how it is carried out is therefore essential. In h aemodialysis, waste solute removal occurs primarily via the principle of diffusion. This is de \201 ned as a type of solute movement across a semi-permeable membrane driven by a con centration gradient (Fig. 3.1.1). This princi- ple is employed by separating an extracorpor eal blood circuit from a \202 ow of specially prepared warmed \202 uid called dialysate by a semi-permeable membrane within a specially designed dialyser (Fig. 3.1.2). The dialys ate is a solution with a solute composition that will minimize the loss of essential solute s such as sodium, calcium, magnesium, chloride, bicarbonate, etc. Fluid loss is achieved by applying a hydrostatic pressure gradient to the blood compartment. Modern dialysis machine s generate the prescribed dialysate composition from a solute concen- trate with puri \201 ed water, and control \202 uid removal by vol- umetric measurement according to the trea tment prescription. Anticoagulation \200 Unfractionated heparin remains the most common agent used for anticoagulation; however, fra ctionated heparin is now being used more commonly. In chronic ESRD dialysis there is usuall y no call for regional anticoagulation of the circuit with little systemic anticoagulation, but this is often necessary in the criti- cally ill. Under these circumstances, protamine can be infused into the venous limb of the circuit to reverse the heparin effect. Citrate a nticoagulation with calcium reversal has now gained favor and reduces the risk of bleeding to a mini- mal level. All forms of regional anticoagulation need careful protocols to run p roperly. In the most severely ill, it may be possible to run the circuit without anticoagul ant at a high blood \202 ow. Dialysers, membranes and biocompatibility Membrane technology has resulted in the hollow \201 bre dia- lyser becoming the standard design. This helps minimize the priming volume of the circuit. Membranes are now available in a range of materials compared with the origina l cupro phane, e.g. polysulphone, polycarbonate, polyacrylo- nitrile. They can be manufactu red with a wide variety of diffusive and hydraulic conductance properties. The only truly b iocompatible surface is normal endothelium, but the modern membranes are less likely to act ivate the alterna- tive complement pathway than the older cellulose-based versions. In gene ral, haemodialysis membranes restrict the passage of solute particles with a molecular weig ht of >500Da. Extracorporeal circuit Access \200 The success of any extracorporeal treatment is 90% dependent upon the quality of the access . Patients with ESRD ideally will have an established surgi- cally created arteriovenous (A V) \201 stula which allows easy access to the circulation. A permanent AV \201 stula is extremely precious and must be protected particularly from prolonged hypotension. It must not be used for any other purpose. In acute renal failure, temporary access to the circula- tion is normally achieved by the insertion of a large bore dual-lumen catheter suf \201 c ient to allow a blood \202 ow of 200ml/min. Factors that in \202 uence solute clearance in dialysis \200 Blood flow. Solute clearance increases as blood flow increases, but normally the rise in cl earance drops off once 250 \200\223300ml/min has been achieved. Poor circuit blood \202 o w has a major limiting effect on dialysis ef \201 ciency Blood To Patient Diffusion Anticoagulant Reversal Semi-permeable Membrane Dialysate in Dialysate out Anticoagulant Pump From Patient Concentration Gradient Blood Fig. 3.1.1 Diffusive transportation. Fig. 3.1.2 Haemodialysis circuit. 65 CHAPTER 3.1 Haemodialysis acute renal failure. Sometimes this may be necessary because the critical care staff may no t be familiar with ESRD haemodialysis techniques. \200 Dialysate \202 ow. Solute clearance is affected by the mainte- nance of the highest solut e concentration gradient across the membrane. A high dialysate \202 ow of 500ml/ min is t he norm in ESRD. Above this level there is little gain in clearance Membrane. The propertie s of the membrane will deter- mine the hydraulic conductivity and the rate of transfer of s olute of any given size. If a high \201 ltration fraction is generated, protein depositio n upon the membrane will reduce hydraulic and solute conductance. Increasing the surface ar ea will raise clearance. The technique used should be adapted to both the patient \200\231s needs and the unit \200 \231s expertise. When should dialysis be started in acute renal failure? The decision of the timing of the s tart of RRT has to be tailored to the needs of the individual patient. Much will depend upo n the cause of the renal failure and whether this has occurred with single organ disease as opposed to multi-organ failure. In the situation of a simple nephrotoxic insult causing no other major organ failure, such as an excess of gentamicin, RRT can be delayed until the u rea is approaching 30mmol/l. Intermittent haemodialysis treat- ment will allow adequate con trol and adequate patient mobilization. In the situation of renal failure secondary to seps is or post-ruptured abdominal aortic aneurysm repair, treatment should be started early and a continuous RRT strategy should be pursued. Adequacy of dialysis For patients with ESRD on chronic dialysis there is a sig- ni \201 ca nt body of data on the adequacy of dialysis and calcu- lation of the dialysis dose using th e Kt/Vurea or urea reduction ratio (URR = 1 \200\223 post-dialysis urea/pre- dialysis urea ). Kt/V represents the fractional clearance of urea. This relates the dialyser clearance (K ) and the time on treatment to the distribution volume of urea. It can be expressed accordi ng to a single or, more accurately, a double pool kinetic model. The difference between pre - scribed and achieved clearance is often signi \201 cant and is in \202 uenced by factor s such as recirculation, lower than expected blood \202 ow and lower ef \201 ciency of t he dialyser than anticipated, e.g. protein adsorption. In ESRD, a KtV value of >1.2 and URR >65% is normally accepted to improve long-term outcome. Even in chronic dialysis practice, it is important to take into account factors other than these calculations alone. There is evidence that the clearance of molecules greater in size than urea and less than albumin, the so-called middle molecules, is important in the prevention of the uraemic syndrome alth ough there is still debate over the identity of the \200\230uraemic \200\231 toxin(s). In acute renal failure there are far fewer data on the best way to estimate the dose for renal replacement therapy (RRT). The patients are seldom in steady state, it is dif \201 cult t o establish a lean body mass and there is com- monly increased protein catabolism following trauma/sur- gery/bleeding. Most will attempt to keep the blood urea below 30mmol/l prior t o commencing the next treat- ment for an intermittent regime and below 20 mmol/l for a cont inuous regime. Continuous or intermittent, fast or slow? Dialysis is highly ef \201 cient at removing low molecular weight solutes. Short intermittent dialysis regimes have been developed over the years for ESRD, and these are probably only suitable for critically ill patients who are s table, nor- motensive, non-catabolic and recovering from the illness precipitating their ad mission to the ICU. This allows them to mobilize and minimizes exposure to anticoagulation. There are also patients in whom rapid solute exchange may be speci \201 cally indicated \200 \200 Life-threatening hyperkalaemia Highly water-soluble low molecular weight poisons with a low volume of distribution, e.g. lithium, ethylene glycol. Contraindications for short duratio n high ef \201 ciency dialysis would include \200 \200 \200 \200 Cerebral injury/oedema Hepatic failure Severe azotaemia (dysequilibration syndrome) Cardiov ascular instability. In these circumstances, the rapid solute change due to the maximum concentration gradient a t the start of high ef \201 ciency dialysis will cause major water shifts into the brain w ith the generation of cerebral oedema. Continuous or semi-continuous methods (e.g. sustaine d low ef \201 ciency dialysis; SLED) should be used in these circumstances with a much slo wer solute transfer to minimize the rate of loss of solute from the blood compartment. In S LED the blood \202 ow and dialysate \202 ow are reduced, which prevents major solute gr adients developing between the intra- and extracellular fluid compartments. This minimizes large water shifts across cell membranes. In reality, with the new dialysers that allow sel ection of the pore size, surface area and hydraulic conductivity, pure diffusive continuous therapies are becoming less common and convective ( \201 l- tration) and diffusive (dialy sis) are now combined as haemodia \201 ltration Buffer Originally acetate was used as the buffer in the dialysate for reasons of chemical s tability, but acetate must be metabolized to bicarbonate and causes vasodilatation, which m akes it unsuitable for the critically ill. With changes in dialysate preparations and the u se of modern machines, bicarbonate is now the buffer of choice for the critically ill and i s also now used in >75% of European chronic dialysis patients. Performing haemodialysis in the critically ill The ESRD patient who develops critical illne ss With the increasing number and age of patients receiving long-term dialysis support, the number presenting for planned or unplanned critical care support is rising. The ESRD patie nt will normally require a longer time on dialy- sis to cope with the increased catabolic l oad in order to prevent complications such as uraemic pericarditis. Preservation of their a ccess is important, and their treat- ment must be managed in conjunction with staff experi- enced in ESRD care. The method of RRT may need to be changed depending upon the acute prob lem, and it may be necessary to use the methods normally preserved for Complications of haemodialysis \200 Hemorrhage from access, line disconnection, anticoag- ulation Thrombosis of the extracorpor eal circuit Air embolism, although this is minimized by modern machines having sophisticate d air detectors for the venous side of the circuit \200 66 A SHORT \200 Fluid overload This may be from limited ability to remove \202 uid on haemodialysis compa red with haemo \201 l- tration Hypothermia from heat loss from the circuit and/or the use of unheated dialysate. Dysequilibration syndrome Electrolyte abnormalities and haemolysis, although these are very rare with modern machinery unless the dia- lysate composition is set incorrectly Anaphylac toid bradykinin reactions (AN69 membranes in patients receiving angiotensin-converting enzy me inhibitors) Pyrogen reactions due to the use of non-pure water Hypovolaemia Further reading http://www.adqi.net/ Ronco C, Bellomo R, Kellum J, eds. Critical care nephr ology. \200 Saunders, 2008. ISBN: 978-1416042525. This page intentionally left blank 68 C RONCO & Z RICCI Haemo(dia) \201 ltration Introduction Despite advances in the understanding, diagnosis and treat- ment of acute kidn ey injury (AKI), many aspects remain unre- solved. Modern technology has provided different modalities to perform extracorporeal renal support, but it is not clear which is superior in terms of ef \201 cacy and outcome. The TMP gradient is the difference between the pressure in the blood compartment and \201 ltrate compartment. The blood compartment pressure is directly related to blood \202 ow (Qb). The \201 ltrate compartment pressure is modulated by suction in modern RRT machines . The machines are designed to maintain a constant rate (Qf): when the \201 lter is \200 \230fresh \200\231 and highly permeable, the pumps retard UF produc- tion, generating a pos itive pressure on the \201 ltrate compart- ment (TMP is initially dependent only on blood \202 ow). As the membrane \201 bres become degraded, a negative pres- sure on the \201 ltrate side is necessary to achieve a constant Qf. With time, TMP progressively increa ses up to a maxi- mum level at which solute clearance is compromised, and clotting of the \201 lter or membrane rupture is possible. The size of molecules cleared during convection and UF exceeds that during diffusion, because they are physically dragged to the UF side; however, this gradually becomes limited by the protein layer that progressively closes \201 lter pores during convective treatments. In addition, the mem- brane itself can adsorb molecules, and this is important for higher molecular weight toxins. The membrane adsorpti ve capacity is generally saturated in the \201 rst few hours of \201 l- ter use and has a relatively minor impact on mass separa- tion processes. During UF, plasma water and solu tes are \201 ltered from the blood, leading to a decrease in blood hydrostatic pressure a nd increase in blood oncotic pres- sure. The fraction of plasma water that is removed from the blood during UF is called the \201 ltration fraction and should be kept in the range of 20 \200\22325% to prevent exces- sive haemoconcentration within the \201 ltering membr ane. Otherwise, the oncotic pressure gradient could neutralize the TMP gradient, resulting in equilibrium. Replacing plasma water with a substitute solution completes the haemo \201 ltration (HF) process. The replacement \202 uid can be administered after the \201 lte r (post- \201 lter dilution HF), before (pre- \201 lter dilution HF) or both. Post- \201 lter dilution leads to a higher urea clearance ( 2000ml/h), but pre- \201 lter dilution p ro- longs the circuit lifespan by reducing haemoconcentration and protein build-up in the \201 lter \201 bres. Conventional HF is performed with a highly permeable, steam-sterili zed mem- brane with a surface area of 1m2. The addition of convection to the diffusion pro cess allows haemodia \201 ltration: dialysis and replacement solutions run simultaneously within the same \201 lter to obtain additional solute removal. Indications to start renal replacement therapy (RRT) RRT is indicated when renal dysfunctio n leads to one or more of the following: \200 \200 \200 \200 \200 Oligo/anuria Severe \202 uid overload Pulmonary oedema Hyperkalaemia Metabolic acidosis However, recent greater ease of use and a low associated morbidity has led to RRT being con sidered early in the dis- ease process. This may be related to the perception that maintena nce of homeostasis and prevention of complica- tions is increasingly important. There is al so some evidence that RRT has some role to play in the management of sep- sis and multi-org an dysfunction syndrome (MODS). Indications to stop RRT There is no hard evidence on how and when RRT should be stopped. It is generally accepted, however, that increas- ing urine output during RRT is a signal that the kidneys are improving. Removal of RRT should also be considered if the patient demonst rates haemodynamic stability with decreased requirement for vasopressors and improving cond ition overall. Principles of renal replacement The kidneys \201 lter the blood to remove excess water an d waste products. Renal replacement essentially uses semi-permeable membranes to achieve th e same result. The membrane may be arti \201 cial, as in a \201 lter, or autologous, as in the peritoneum. Many molecules, including water, urea and solutes of various molecular w eights, are transported across the membrane by variable combinations of the processes of di ffusion (dialysis) and convection (ultra \201 ltration (UF)). During diffusion, the moveme nt of solutes depends on their tendency to reach the same concentration on each side of the membrane; this results in the passage of solutes from the compartment with the higher conc entration to the compart- ment with the lower concentration. Diffusion is affected by chara cteristics of the semi-permeable membrane including thickness, surface area, temperature an d diffusion coef \201 cient. Diffusion is provided by dialysis, in which a solution (the d ia- lysate) \202 ows on the other side of the membrane, counter- current to blood \202 ow, in order to maintain a solute gradient. In convection, the movement of solute across a semi-per- meable membrane is a result of transfer of water across the membrane. In other wo rds, as the solvent (plasma water) crosses the membrane, solutes are carried with it if the pore size of the membrane allows. Convection can be achieved by UF, which creates a transm embrane pressure (TMP) gradient. UF depends on the rate of \202 ow (Qf), the membrane coe f \201 cient (Km) and the TMP gradient between the pressures on both sides of the membrane : Choice of mode RRT may be intermittent or continuous. In general, inter- mittent RRT is res erved for haemodynamically stable patients. How effectively RRT is applied may be more impo rtant than the method chosen. It is dif \201 cult to use biochemical or clinical markers t o monitor RRT. Urea con- centration should be <30mg/dl and creatinine <221 mol/l. Nonethel ess, urea and creatinine clearance do not neces- sarily represent the clearance of other to xins and solutes. The ideal RRT would include: \200 ef \201 cient solute removal \200 minimum solute disequilibrium \200 low UF rate \200 haemodynamic stability \200 low a nticoagulant needs \200 minimal interference with patient mobility Qf = Km \227 TMP 69 CHAPTER 3.2 Haemo(dia) \201 ltration produced during membrane transit is in excess of the patient \200\231s desired weight loss, and replacement solution is needed to maintain \202 uid balance. Solute clearance is bot h convective and diffusive. Circuit blood \202 ow: 100 \200\223250ml/min Dialysis \202 ow: 15 \200\22360ml/min Ultra \201 ltrate rate: 15 \200\22360ml/min. Continuous RRT schedule may be adjusted to ful \201 l the patients needs and the illness. Practical RRT prescription During RRT, clearance (K) depends on circuit blood \202 ow (Qb ), haemo \201 ltration \202 ow (Qf) or dialysis \202 ow (Qd), the molecular weight of the solutes, and th e \201 lter type and size. Circuit blood \202 ow is mainly dependent on vascular access and operational characteristics of the machines. In haemo \201 ltratio n, Qf is strictly linked to Qb by the \201 ltra- tion fraction. In dialysis, however, Qd is not limited by the \201 ltration fraction, but when the Qd/Qb ratio exceeds 0.3 dialys is will be less ef \201 cient. Urea and creatinine are gener- ally used as reference solut es in order to measure the effectiveness of the RRT prescription, but their clearance is no t directly correlated with outcome of AKI. High volume haemo \201 ltration (HVHF) This treatment uses highly permeable membranes and haemo \201 ltration with a high volume setting: Qb >200ml/ min and Qf >45ml/kg/h in order to increase removal of high molecular weight solutes (such as sepsis and systemic in \202 ammatory mediators). Anticoagulation In many RRT modalities blood comes into contact with the arti \201 cial su rfaces and some form of anticoagulation is needed. To reduce the risk of the \201 lter cl otting, vascular access should be of adequate size, kinked tubing should be avoided and the blood \202 ow rate should exceed 100ml/min. Pump \202 ow \202 uc- tuations must be p revented (in modern machines this is mainly due to circuit increased resistances rather tha n \202 ow rate inaccuracies). Venous bubble traps, where air \200\223blood contact occurs , are used to prevent systemic air emboli, and the machine will alarm if bubbles are detect ed. There is evidence that when the set-up is perfectly opti- mized, anticoagulants contrib ute little to the maintenance of circuit patency. When anticoagulants are relatively con- t raindicated (risk of bleeding, pre-existing coagulopathy, thrombocytopenia) RRT can still b e safely performed and \201 lter life may not be compromised. Unfractionated heparin is t he most commonly used antico- agulant. The dose ranges from 5 to 10IU/kg/h. In some patient s, heparin can also be used in combination with pro- tamine administration post- \201 lter (regional heparinization) with a 1:1 ratio (150IU of unfractionated heparin per mg of prot amine) and monitoring of prothrombin time (aPTT). Problems with heparin are relatively unpr edictable bioa- vailability, antithrombin III depletion and the risk of heparin- induced th rombocytopenia (HIT). Low molecular weight heparins are used in some units, but prospective studies have not yet shown them to be supe- rior in prolonging circuit life. Bioavailabili ty is more reliable than unfractionated heparin, and the risk of HIT is lower. However, the anticoagulant effect cannot be reversed and there may be a higher risk of hemorrhage. Pros tacyclin is potentially useful for RRT anticoagulation, being a potent inhibitor of platele t aggregation with a short half-life. It is infused at a dose of 4 \200\2238ng/kg/h with or with- out the adjunct of low dose heparin. Hypotension may be induced by higher doses. Hig h cost and the risk of hypoten- sion limit the use of this agent to short-term treatment. C itrate chelates calcium to prevent clot formation and can produce regional anticoagulation. Administration of cal- cium chloride may be required to maintain normocalcae- mia. This ap proach is effective in maintaining \201 lter patency and compares favorably with heparin. It also avoids the risk of HIT and does not lead to systemic anticoagulation. However, the risk of hypocalcaemia, metabolic alkalosis and the cumbersome replacement and dialysate \202 uid prep- aration limit its use. Membrane sieving coef \201 cient (SC) During UF, the driving pressure jams solutes, such a s urea and creatinine, against the membrane. The SC determines the amount of solute that pa sses through the pores of the membrane. The SC is calculated by the ratio of the con- centr ation of the solutes in the \201 ltrate to that in the plasma. An SC of 1.0, as is the ca se for urea and creatinine, demon- strates complete permeability and a value of 0 total imp er- meability. Molecular size (<12Da) and \201 lter porosity are the major determinants o f SC. During continuous treat- ments, a minimum urea clearance of 30ml/h/kg (2.8l/h in a 70 kg patient) is required. Techniques Slow continuous ultra \201 ltration (SCUF) Blood is driven by a pump through a highly permeable \201 lter via an extracorporeal circuit, using venovenous access. The ul trafiltrate produced during membrane transit is not replaced and it corresponds to weight l oss. It is used only for \202 uid control in overloaded patients Circuit blood \202 ow: 100 \200\223250ml/min. Ultra \201 ltrate \202 ow: 5 \200\22315ml/min. Continuous venovenous haemo \201 ltration (CVVH) CVVH is similar to SCUF above except that the ultra \201 l- trate produced during membrane transit is partly or com- pletely replac ed to maintain intravascular volume control. Replacement \202 uid may be delivered before , after or on both sides of the \201 lter (pre- or post-dilution). Clearance for all solu tes is convective and equals the UF rate. Circuit blood \202 ow: 100 \200\223250ml/min. U ltra \201 ltrate rate: 15 \200\22360ml/min. Continuous venovenous haemodialysis (CVVHD) In CVVHD, blood is driven through a low permeab ility dia- lyser via an extracorporeal circuit in venovenous mode and a counter-current \202 ow of dialysate is delivered on the dia- lysate compartment. The ultra \201 ltrate pr oduced during membrane transit corresponds to the patient \200\231s weight loss. Solute cle arance is mainly diffusive, and ef \201 ciency is limited to small solutes only. Circuit b lood \202 ow: 100 \200\223250 ml/min. Dialysis \202 ow: 15-60 ml/min. Continuous venovenous haemodia \201 ltration (CVVHDF) This is a technique where blood is d riven through a highly permeable dialyser via an extracorporeal circuit in veno- venous mod e and a counter-current \202 ow of dialysate is delivered on the dialysate compartment. T he ultra \201 ltrate 70 A SHORT Peritoneal dialysis (PD) There are reports of the \201 rst PD being performed in the mid 18th century; however, it was not until the 1920 \200\2231930s that the treatment was re-introduced experimentally f or acute renal failure. It began to \201 nd some favor in the late 1940s, but was dogged by the problem of peritonitis and access problems. Since the 1970s, continuous ambulatory p eritoneal dialysis (CAPD) has been a common form of ESRD therapy, particularly for those wi th some residual renal function for whom it can be used for many years or where there are c ontraindications to anticoagulation. Many patients ultimately have to move to haemodialysis in order to achieve adequate control of azotaemia. However, prior to this, intermittent PD was a relatively common method used for the management of acute renal failure or as a (les s than ideal) bridge until a place was found on a chronic haemodialysis program. Other than the lack of need for anticoagulation, the main advantages of PD is that the peri- toneum i s a natural semi-permeable membrane and that the process can be continuous. CAPD allows nea r normal patient mobility These frequently caused leakage, infection was common and the risk of visceral damage high, but nowadays silastic catheters based upon the design of Tenckhoff and Schechter are used which are tunneled subcutaneously and have Dacron cuffs placed subcutaneously. These may be inserted via a trochar and cannula, mini- laparotomy or minilaparoscope even at the bedsid e. The proper positioning of the catheter is essential to ensure ef \201 cient drainage an d function of the catheter. Simple issues such as constipation may signi \201 cantly affec t catheter function. Previous abdominal surgery with the likelihood of multiple adhesions i s a relative contraindication for PD Techniques PD is carried out by \201 lling the peritoneal cavity with sterile pre-prepare d dialysate fluid. The peritoneal fluid will achieve solute equilibration with the plasma w ater in 4 \200\2235h, although the optimum dwell time for maximum \202 uid removal using dextrose as the osmotic agent is 2 \200\2233h. The \202 uid is then drained and replaced with fresh dialysate. A single \201 lling and draining of the peritoneal cavity is called a cycle. The commonly used CAPD popularized in the late 1970s for ESRD management uses lon g dwell times and 4 \200\2235 cycles per day, 7 days per week. The patient drains and re \201 lls the peritoneal cavity, taking 30 \200\22340min, at intervals throughout the day. T he ef \202 uent bags are weighed to determine the volume of \202 uid removed and the con centra- tion of osmotic agent adjusted to keep the patient \200\231s \202 uid balance neu tral. Some patients use machines that cycle on a shorter time basis through the night. Thes e remove the need for inconvenient bag changes, warm the dialysate and can be programmed fo r targeted \202 uid removal. The abdo- men can be left empty or full throughout the day. The method used will depend upon the method availability, individual circumstances and the wishes of the patient. Peritoneal membrane structure and solute transfer The three-pore model of the peritoneal me mbrane accounts for \200 the measurable, but low, rate of transfer of proteins through a small number of large pores >15nm some convection with solvent drag (osmotic gradient) through water channels, 0.5nm ( aquaporins) diffusive solute movement (concentration gradient) through the large number of 4nm pores allowing small solute and water passage.