ALS or BLS

[Savoy6]

There was no personal attack involved. Everyone here should know that even at 'their stable base-line' a dialysis pt is one of the most sick and complicated we can encounter as clinicians in medicine. Fact of the matter is just the dialysis treatment itself can soemtimes cause metabolic and physiologic problems. Now compund that with a 10-20% total volume Blood loss. This patient clearly needs ALS asessment and potentially interventions to treat co-comittant 'disorders' which are or could be occuring with this patient. The patient recieveing early beneficial care which is unavailable for the average basic to provide is what is important here. Furthermore there is so much rationale I could post loads of info about it. This patient warrants ALS, there is no question. If you need for me to post more info on dialysis and renal failure, and or point you in the direction of some sources to get you started I will be more than happy to. Furthermore, I would expect you as a long time member of this site to know better than to think this is about being X mins for a hospital and more about providing your patient with access to appropriate timely treatment as well as continuing care.

Out here,

ACE844

See, a rationale. But my question was not answered.

Thanks for the offer of the info. See how this snide comment appears. you do not know me, nor my level of expertise, yet you take it upon yourself to enlighten me on what patient care is about. I do appreciate the offer.

It is because of this that many providers I know leave this site. This stifles open discussions and drives folks away. We are a long way from a profession when discourse does become personal--"Furthermore, I would expect you as a long time member of this site to know better than to think this is about being X mins for a hospital and more about providing your patient with access to appropriate timely treatment as well as continuing care" if that isn't personal, what is it.

i like to see if people can use rational thought and not emotional responses. Keeps discussions flowing, and I'm not trolling.

Good bye. Good luck.

[Ace844]

See, a rationale. But my question was not answered.

Thanks for the offer of the info. See how this snide comment appears. you do not know me, nor my level of expertise, yet you take it upon yourself to enlighten me on what patient care is about. I do appreciate the offer.

It is because of this that many providers I know leave this site. This stifles open discussions and drives folks away. We are a long way from a profession when discourse does become personal--"Furthermore, I would expect you as a long time member of this site to know better than to think this is about being X mins for a hospital and more about providing your patient with access to appropriate timely treatment as well as continuing care" if that isn't personal, what is it.

i like to see if people can use rational thought and not emotional responses. Keeps discussions flowing, and I'm not trolling.

Good bye. Good luck.

It wasn't an attack but a reference to the NUMEROUS discussions we have had here about EMS treatment, efficacy, and definative care, etc... As a long time member here you have had the ability and even soemtimes participated in these, hence my comment. :roll: That was what the comment was referencing. I cannot control how you choose to interpret this, but I can further clarify and explain as I have just done...Lastly, this is a basic 'tenet' of medicine, something that should not be new to all but the most newest of 'rookies' and even then this should have been soemthing covered in their program. (BY that I mean that Dialysis pt's are by their nature unstable and sick pts, like I mentioned in my post)

Out Here,

ACE844

[Savoy6]

Lastly, this is a basic 'tenet' of medicine, something that should not be new to all but the most newest of 'rookies'

What basic tenet are you refering too? let it go, you can't stop yourself. Go back to you playground and share these antics with the other boys and girls. It is very easy for this holier than thou attitude that is prevelant on this site. preach to someone else,not to me. I do not need a lesson from you.

I guess I am a heretic. Go and sin some more.

Please do not reply. I will not be here.

I'm looking for a site that when opinions are asked for they will be respected. This bovine scatology is good for rookies and the others on this site that all refer to as wankers. i myself like to use that term to describe this in the same way as our British cousins.

[PRPGfirerescuetech]

PR:

If this were you and me on a truck I'd take it. Blood loss, a rate in the 70s, some BP changes on position all post dialysis would have me just slightly concerned. Even if this were a larger patient I'd still be concerned with the blood loss and lack of a tachy rhythm.

Did I miss it? You mentioned a complete treatment. How long was she hooked up?

And do I really have to guess with whom you were working on this call? I can guess, you know. In fact, I have a pretty good idea of who it might've been.

And let me guess further, she had you take it.

-be safe.

4 hour treatment.

Suprisingly, different organization, although I did chuckle at the likelyhood that she would be the one. It was a new medic, we were on our 12th? call, he saw blood and a "normal" blood pressure, regardless of change from their baseline, and kicked it BLS.

To everyone, great responses. This is a baseline call that could go either way for several reasons.

[PRPGfirerescuetech]

For all those who responded ALS, please, without cutting each others modalities up, outline what your treatment regiment is going to be for the ten minute transport to the hospital. Ive got a point for this, bear with me....

[Ace844]

I already mentioned most of my management, but I also have another question for you. Because this is a new graft does the pt still have a triple lumen central line in place, if so where, and is it patent?

ACE844

[PRPGfirerescuetech]

I already mentioned most of my management, but I also have another question for you. Because this is a new graft does the pt still have a triple lumen central line in place, if so where, and is it patent?

ACE844

Great question. Central line removed the day before.

[Ace844]

Great question. Central line removed the day before.

This can make a big difference in treatability, as Dialysis pt's are notoriously difficult to get large bore or even small bore patent Iv lines in. Was this your point? No line, no fluid, etc...? ALso another follow up questin for ya. Does your systemt allow you to access the shunt? If not, did the pt still have the dialysis cath in when they hemmorraged?

ACE844

[Ridryder 911]

For one thing, check the the "thrill " of the shunt. Bolus her with 250 ml of NSS, and watch for impending s/s of overload. Monitor her because of her baseline hypovelemia and underlying medical conditions needs to be. If this patient was not a CRF and did not have a major underlying medical problems, then yes maybe a basic call because the body could compensate and there would be no problems.

Since this patient already has a major illness, one needs to assess in detail. It is irrelevant what the initial vitals were, she is symptomatic with tilt and obvious hemorrhage on the ground. Look at the PMHX, medication's, etc.. this is the differential in making a BLS versus an ALS.

R/r 911

[Ace844]

Lastly, this is a basic 'tenet' of medicine, something that should not be new to all but the most newest of 'rookies'

What basic tenet are you refering too? let it go, you can't stop yourself. Go back to you playground and share these antics with the other boys and girls. It is very easy for this holier than thou attitude that is prevelant on this site. preach to someone else,not to me. I do not need a lesson from you.

I guess I am a heretic. Go and sin some more.

Please do not reply. I will not be here.

I'm looking for a site that when opinions are asked for they will be respected. This bovine scatology is good for rookies and the others on this site that all refer to as wankers. i myself like to use that term to describe this in the same way as our British cousins.

"Savoy6,"

Just for you and in case you may not have had the opportunity to be exposed to this information in your EMS career let's take a look and see what THE TEXT in Nephrology practice and ed. has to say(***Note: This is depending on the biases of the attendings and professors in your residency and medical school**) Also contained below is in part the 'why' of 'why' dialysis patients are considered among the sickest you can clinically treat. ALso below I've included the pathogenesis as to why this patient is ALS 2nd to hemmhorrage concerns..

(Brenner & Rector's The Kidney @ 7th ed., Copyright © 2004

Chapter 59 - Hemodialysis

Gerald Schulman

Jonathan Himmelfarb)

THE HEMODIALYSIS POPULATION

Demographics

For more than 300,000 patients in the United States who have reached end-stage renal disease (ESRD), hemodialysis has become a routine therapy. However, it should not be forgotten that this lifesaving treatment has been routinely applied for ESRD only for the past 30 years. Beginning with the successful experiments by Abel and colleagues,[1] it was shown that when blood was circulated through numerous collodion tubes surrounded by a jacket containing dialysis fluid, substances diffused from the blood to the dialysate. The investigators also demonstrated that the composition of the dialysate fluid was a major determinant of what was removed or retained during the procedure. Based on these findings, Kolff developed the rotating drum artificial kidney, which rapidly found use in treating patients with acute renal failure.[2] Pioneering physicians such as Merrill, Scribner, and Schreiner successfully supported patients through the oligoanuric phase of acute renal failure. Teschan introduced hemodialysis to the battlefield during the Korean War.

Successful application of labor-intensive and technically demanding hemodialysis to acute renal failure was accomplished in the acute care setting. However, adaptation of the acute procedure to the management of permanent, irreversible renal failure required the intersection of a number of medical and social developments that led to the creation of an infrastructure capable of supporting the current ESRD program. A major issue was finding a method of reliably and repeatedly entering the patient's circulation to perform the treatment. The use of an external bridge or shunt connected to an artery and vein in the wrist was championed by Scribner for use in acute renal failure and could be used in treating chronic renal failure, although with great difficulty because of infection and repeated episodes of clotting. It was

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2564

then demonstrated that an internal connection between the radial artery and distal cephalic vein in the wrist (i.e., Cimino fistula) could be hemodynamically tolerated. The vein returning blood under high pressure eventually became "arterialized" and allowed repeated access to the circulation. Internal connections between suitable veins and arteries that were not near each other were accomplished with the use of bovine venous grafts or artificial tubing. Mass production of disposable devices for the treatment, such as dialyzers, tubing, and easily reconstituted dialysate, was also required to enable the widespread application of maintenance hemodialysis.

The last of the necessary pieces required for delivery of dialysis was the will of the nation to allow a sufficient portion of its health care funding to be dedicated to treating for an indefinite period a chronic, unremitting process such as ESRD. Until such a decision was made, hemodialysis for ESRD was an expensive and inefficient procedure. Often, it was made available by the decision of a selection committee who chose only the young who were free of comorbid conditions. Employment and level of education were important criteria for selection. However, after much debate in the lay and medical communities, in 1973, the U.S. Congress passed the law entitling Medicare patients to dialysis and transplantation treatments.[3] Perhaps as a legacy of the restrictive acceptance policies before entitlement, the initial estimate of the numbers of patients who would enter the ESRD program was low. This legislation eventually evolved to provide care for patients with ESRD irrespective of means, education, employment, or other medical conditions. The ESRD entitlement legislation represents a landmark providing life-sustaining therapy, and no similar program has been proposed for any other chronic disorder.

Incidence and Prevalence of Hemodialysis Patients in the United States

The United States Renal Data Survey (USRDS), the annual registry of the ESRD patients of the United States, indicates that as of December 31, 1999, the annual incidence of hemodialysis patients is 259.8 per 1 million people.[3] This represents 71,426 patients per year. Figure 59-1 demonstrates that the incidence is not uniform across the nation.

The highest incidences appear across the South and West. These areas correspond to regions of the nation having a high incidence of patients with diabetes, the most common cause of ESRD. These regions have high numbers of black and Hispanic American patients, with ESRD incidences of 843.1 per 1 million people and 582.5 per 1 million people, respectively. Figure 59-2 shows that the increasing numbers of patients are reaching ESRD due to diabetes and, to a lesser extent, hypertension. The incidence due to glomerulonephritis and cystic disease has remained constant over several years.

The prevalence of ESRD patients treated with hemodialysis is 758.8 per 1 million people. The prevalence rate for blacks with ESRD is approximately four times that of the general population and 6.5-fold the rate for whites. More than 40% of the ESRD patients have been diagnosed with diabetes, 28% with hypertension, 11.6% with glomerulonephritis, and 4.7% with cystic or other urologic conditions.

Outcomes: Morbidity and Mortality of Hemodialysis Patients in the United States

Figure 59-3 shows that over the years, the number of comorbid diseases in patients at initiation of therapy has increased. Patients initiated on hemodialysis have more comorbidities than patients who are initiated on peritoneal dialysis. Hemodialysis patients are more likely to have cardiovascular disease (i.e., congestive heart failure, ischemic heart disease, or myocardial infarction), cerebral vascular disease, peripheral vascular disease, and chronic lung disease. An important exception is that a higher percentage of insulin-dependent diabetics are initiated on peritoneal dialysis. These differences in the population must be taken into account when comparing the two modalities.

The number of hospitalizations and hospital days per patient-year serve as indices of patient morbidity. In 1999, a total of 1937 admissions for hemodialysis occurred per 1000 patient-years. Hospital days per patient-year for hemodialysis patients averaged 13.9 days in the year 2000. These rates have remained fairly stable over the past 5 years. Admission rates per patient-year at risk are significantly influenced by patient vintage. For all incident and prevalent hemodialysis patients, admission rates are highest for those with less than 1 year on dialysis. Admission rates decrease as the number of years on hemodialysis increases. For incident patients, the risk for a first hospitalization was greater for patients with the lowest hematocrits (<30%) and lowest hemodialysis dose (urea reduction ratio <60%). Admissions for cardiovascular and infectious complications also negatively correlated with hematocrit level and hemodialysis dose. Clinical indicators of care influence patient outcomes.

In 1999, 66,964 patients enrolled in the ESRD program died. This represented an annual mortality rate of 182 per 1000 patient-years at risk for the ESRD population. For hemodialysis patients and peritoneal dialysis patients, the mortality rates were 247 and 231 per 1000 patient-years at risk, respectively. In the past decade, a modest decline in the mortality rate has occurred in all age groups, except in the youngest group (i.e., 0 to 19 years old). Cardiovascular disease and infections account for most deaths. The mortality rates associated with hemodialysis are striking and indicate that the life expectancy of patients entering into hemodialysis is markedly shortened. At age 60, a healthy person can expect to live for more than 20 years, whereas the life expectancy of a 60-year-old patient starting hemodialysis is closer to 5 years.

A recurrent controversy is whether peritoneal or hemodialysis represents a superior form of depuration. The question is difficult to answer with certainty because selection for the two therapies is not random and subject to selection bias. In the past 5 years, the number of patients receiving peritoneal dialysis has remained fairly stable at 20,000 to 27,000, whereas the hemodialysis population has continued to increase. In 1999, only 10% of the dialysis population was treated by peritoneal dialysis.[4] Figure 59-4 demonstrates that in the first year of treatment for ESRD, survival of peritoneal dialysis patients is superior to that of hemodialysis patients. However, in subsequent years, the survival rate is greater for patients receiving hemodialysis. The reasons for

Figure 59-4 Survival on hemodialysis and peritoneal dialysis

TABLE 59-1 -- Classification of Chronic Kidney Disease STAGE DESCRIPTION GFR (mL/min/1.73m2 ) ACTION

1 Injury, not acute, with preserved GFR >90 Diagnose and treat, slow progression, ?comorbid conditions, decrease cardiovascular risk

2 Mild kidney damage 60–89 Estimate rate of progression

3 Moderate 30–59 Treat complications, ESRD education

4 Severe 15–29 Prepare for ESRD treatment

5 Kidney failure <15 Initiate ESRD treatment

GFR, glomerular filtration rate.

Data from National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification and stratification. Am J Kidney Dis 39:S1–S266, 2002.

this finding have not been established. Loss of residual (native) kidney function, which correlates with mortality for peritoneal dialysis patients, has been suggested as a factor. Nevertheless, there are many issues of lifestyle that outweigh gross survival statistics in choosing one modality over the other.

TRANSITION FROM CHRONIC KIDNEY DISEASE TO HEMODIALYSIS

The knowledge that many patients enter into treatment for ESRD with comorbid conditions, particularly cardiac and vascular complications, and have a strikingly higher mortality rate than that of the general population led to the realization that these conditions often begin much earlier, at a time when chronic renal insufficiency has just been identified. In patients who are at risk for a progressive, inexorable decline in glomerular filtration, measures should be undertaken as early as possible to correct the common abnormalities associated with chronic kidney disease (CKD) to reduce comorbidity and allow a smooth transition to hemodialysis. To this end, the National Kidney Foundation has created the Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for CKD, a term chosen to be readily understood by patients and physicians.[5] Regardless of the primary cause, CKD is categorized as one of five stages based on the glomerular filtration rate (GFR) and an action plan ( Table 59-1 ).

Cardiovascular risk factors should be assessed as early as possible, and treatment should be instituted to prevent complications. Education should be provided sufficiently early so that permanent vascular access can be ready for use when the patient reaches ESRD. This is particularly important if the patient chooses hemodialysis. A Cimino fistula offers a number of advantages, including lower rates of thrombosis and infection. However, the veins arising from the fistula often require a number of months to become sufficiently enlarged and thickened so that they can be easily cannulated and provide adequate blood flow. There is also a chance that a fistula will not develop and that an entirely new alternative access plan will have to be developed. This can be a time-consuming process that, if not initiated early enough, may result in the patient reaching ESRD before the access site is mature. The undesirable consequence is the need for a percutaneous catheter, with its much higher risks of infection, thrombosis, and poor function, to bridge the interval between treatment initiation and the creation of a working, permanent access. Whenever possible, in patients with documented progression, a working, permanent hemodialysis access should be in place by the time the GFR falls below 20/mL/minute.

Reducing Comorbidity

In K/DOQI, 15 guidelines have been promulgated regarding the evaluation, classification, and management of CKD. These guidelines are aimed at correcting or modifying the common abnormalities that are found as renal disease progresses to reduce comorbidity in the ESRD population. Optimal pre-ESRD management includes strategies aimed at preventing or slowing progression by identifying those who have CKD and initiating appropriate care with dietary management, blood pressure and glycemic control, and blockade of the rennin-angiotensin-aldosterone system; preventing complications of uremia such as anemia, renal osteodystrophy, and malnutrition; and preparing the patient for the advent of ESRD with education concerning the available treatment modalities, planning for the creation of a permanent access for hemodialysis to avoid the use of temporary catheters, and planning for hemodialysis initiation before major symptoms of uremia arise.

Comorbid conditions that often coexist in patients suffering from renal disease must also be treated. The measures undertaken to treat the complications of CKD often modify the course of these comorbid conditions. Examples of this phenomenon include regression of left ventricular hypertrophy when erythropoietin is used to treat the anemia associated with renal failure and the suggestion that the calcium content in the vasculature partly depends on the type of phosphate binder used in the treatment of osteodystrophy.

Multiple lines of evidence suggest that the patient's health status at the time of initiation of dialysis affects subsequent morbidity and mortality. Protein intake often falls spontaneously as renal function deteriorates.[6] This can lead to a loss of muscle mass and lower serum albumin levels. The serum albumin level at treatment initiation of is a powerful predictor of subsequent mortality. Patients beginning hemodialysis with an albumin level of 3.0 to 3.5 g/dL have a 20% greater annual mortality rate than patients with an albumin level of 3.5 to 4.0 g/dL. Cardiovascular diseases, the greatest cause of mortality in the hemodialysis population, most often begin long before dialysis is initiated. Untreated or inadequately treated anemia may lead to worsened left ventricular hypertrophy and exacerbation of angina as the patient approaches ESRD.[7] [8] [9] [10]

The best approach to treating complications of uremia and comorbid conditions is to identify patients early. Unfortunately, susceptible populations are not always screened for the presence of renal disease.[11] Agents such as angiotensin-converting enzyme (ACE) inhibitors are not always used, and the level of blood pressure control achieved is suboptimal. Education of patients with CKD is often lacking. This leads to little dietary instruction, poor planning for the creation of dialysis access, and failure of patients to avoid potential nephrotoxins.

Initiation of Hemodialysis

Common indications for initiation of hemodialysis in acute renal failure include uncontrolled hypertension, pulmonary edema, acidosis, hyperkalemia, pericarditis, encephalopathy, and elevated levels of blood urea nitrogen (BUN) and creatinine. These indications should never be reasons for initiating chronic maintenance hemodialysis. Occasionally, a patient presents with manifestations of the acute uremic syndrome because of lack of prior medical attention or denial. However, the goal for the patients is a smooth transition from CKD to ESRD.

Referral to Nephrologists

Input from a nephrologist should be obtained after CKD has been identified. The frequency of visits increases as renal function declines. There is emerging evidence that referral to nephrology influences the time at which dialysis is initiated and subsequent outcome. In patients who are followed by nephrologists, dialysis is initiated at a creatinine concentration as much as 4 mg/dL lower than that of patients who have had no medical care. Multiple lines of evidence support the finding that the timing of referral to the nephrologist influences outcome and cost of dialytic therapy.[12] [13] [14] [15] [16]

Patients referred to nephrology less than 1 month before requiring dialysis are more likely to be hypertensive and have congestive heart failure, have marked abnormalities in their serum laboratory values, have lower serum albumin levels, and have markedly longer periods of initial hospitalization. Cost of treating the late referrals is sixfold greater than for patients referred earlier in their course. Each of four studies demonstrates increased mortality after dialysis has started in patients who were referred to nephrology late in their course. It is important to encourage referral to nephrology early in the course of chronic renal failure to prevent complications of uremia.

Starting Hemodialysis

Hemodialysis should be initiated at a level of residual renal function above which the major symptoms of uremia usually supervene. Among the criteria for initiating dialysis recognized by the funding entity for dialysis in the United States are residual creatinine clearances of 15 mL/minute and 10 mL/minute for diabetics and nondiabetics, respectively. K/DOQI guidelines suggest that dialysis should be initiated at a creatinine clearance between 9 and 14 mL/minute.[5] The determination of an adequate dose of hemodialysis is discussed subsequently. With current hemodialysis technology, thrice-weekly sessions of 5 hours each can achieve the equivalent urea clearance of approximately 20 mL/minute in a 70-kg individual.

The government guidelines of creatinine clearances of 15 mL/minute and 10 mL/minute or of serum creatinine concentrations of 6 mg/dL and 8 mg/dL for diabetics and nondiabetics, respectively, are reasonable criteria for initiating hemodialysis. It may be necessary to initiate patients even earlier in their course if they have otherwise uncorrectable symptoms or signs of renal failure such as nausea and vomiting, weight loss, intractable congestive heart failure, or hyperkalemia. After the creatinine clearance falls below 20 mL/minute the patients should be periodically questioned regarding symptoms related to nutrition: loss of appetite; nausea or vomiting, or both, especially in the morning due to overnight retention of uremic toxins in the gut; and unintended weight loss. These are very often the earliest markers of uremia. Asterixis, restless leg syndrome, and a reversal of the sleep-wake cycle are early neurologic manifestations of uremia. If alternative explanations for these symptoms and signs cannot be discerned, they should be considered as indications for initiating dialysis.

VASCULAR ACCESS

History

The use of hemodialysis for the treatment of patients with acute renal failure was introduced by Kolff in 1943 with temporary access to the circulation. [17] However, the development of maintenance hemodialysis therapy for the treatment of ESRD requires repeated access to the circulation. This was not feasible until the introduction of the external arteriovenous Quinton-Scribner shunt in 1960.[18] The Quinton-Scribner shunt was made of silastic tubing connected to a Teflon cannula. The Quinton-Scribner shunt developed frequent problems with thrombosis and infection, and it typically functioned for only a period of months. In 1966, Brescia, Cimino, and others developed the endogenous arteriovenous fistula, which remains the access of choice for maintenance hemodialysis today.[19] The unfeasibility of developing functional native arteriovenous fistulas in all patients led to the development of interpositional bridge grafts in the late 1960s and 1970s. Initial graft biomaterials consisted of autogenous saphenous veins, bovine carotid arteries, and human umbilical veins. In the late 1970s, synthetic bridge grafts made of expanded polytetrafluoroethylene (ePTFE) were introduced.[20] [21] The ePTFE grafts can be placed in most patients, are usable within weeks of surgical placement, and are relatively easy to cannulate. The ePTFE grafts remain the most frequently used graft biomaterial today and continue to be the type of permanent dialysis access most frequently placed in the United States.

Although the relative advantages and disadvantages of each type of permanent dialysis access are discussed further, it is clear that native vein arteriovenous fistulas are preferable to all other vascular access options. Current clinical practice guidelines recommend the radiocephalic primary arteriovenous fistula as the access of choice, followed by the brachial-cephalic primary arteriovenous fistula. Patients with CKD should be referred for a surgical attempt to create a primary arteriovenous fistula when the creatinine clearance falls below 25 mL/minute, when the serum creatinine level is greater than 4 mg/dL, or within 1 year of the anticipated need for maintenance dialysis therapy.

The use of catheters for hemodialysis access also parallels the history of dialysis itself. In 1961, Shaldon and colleagues first described femoral artery catheterization for hemodialysis access.[22] In 1979, Uldall and associates first reported the use of guidewire exchange techniques and subclavian vein puncture for placement of temporary dialysis catheters.[23] In the late 1980s, the use of surgically implanted, tunneled, cuffed, double-lumen catheters was introduced.[24] Subcutaneous vascular ports were introduced as an alternative to the cuffed, tunneled catheter.[25] Although the major use of catheters for hemodialysis access is as a bridging device to allow time for maturation of a more permanent access or for patients who need only temporary vascular access, catheters are increasingly being used for permanent vascular access in patients for whom all other options have been exhausted.[26]

Although there have been impressive technical improvements in hemodialysis vascular access, none of the available types of vascular access meet the performance characteristics required for "perfect" vascular access (see Table 59-1 ). Vascular access continues to be referred to as the "Achilles heel" of the hemodialysis procedure.[27] Vascular access complications are responsible for considerable cost, morbidity, and mortality in the patient population on maintenance hemodialysis.

Epidemiology

The rapid growth of end-stage renal failure programs in the United States and worldwide has been accompanied by a tremendous increase in dialysis vascular access-associated morbidity and cost.[27] The creation, maintenance, and replacement of vascular access in hemodialysis patients is recognized as a major source of morbidity and cost within the U.S. ESRD Program, with estimates that costs probably exceed $1 billion within the Medicare program on an annual basis.

There is compelling evidence that there are large differences in patterns of vascular access usage between Europe and the United States. The Dialysis Outcomes and Practice Patterns Study (DOPPS) compared vascular access use and survival in Europe and the United States.[28] Native arteriovenous fistulas were used by 80% of European patients, compared with 24% of prevalent dialysis patients in the United States. Arteriovenous fistula use was significantly associated with male gender, younger age, lower body mass index, absence of diabetes mellitus, and a lack of peripheral vascular disease. However, even after adjusting for these risk factors, the odds ratio for arteriovenous fistula use in Europe versus the United States was 21. Enormous facility variation also occurs in the United States, with the prevalence of arteriovenous fistulas ranging from 0% to 87%.[28] A follow-up study from DOPPS suggests that predialysis care by a nephrologist does not account for substantial variations in the proportion of patients commencing dialysis with an arteriovenous fistula and that the time to fistula cannulation after creation also varies greatly between countries.[29] Practice pattern variations in vascular access care are not entirely associated with patient-related factors; the processes of care also influence these variations.

The importance of vascular access care has been emphasized by data from the USRDS demonstrating that adjusted relative mortality risk is substantially higher for patients with central venous catheters than for arteriovenous fistulas in diabetic and nondiabetic patient populations.[30] For diabetic patients, the use of arteriovenous grafts is also associated with significantly higher mortality risk compared with arteriovenous fistulas; infectious and cardiovascular causes are implicated in these cases.

Data from Medicare and the USRDS indicate that the prevalence of arteriovenous fistula use is increasing in the United States. The increase in fistula placement coincides with the publication of K/DOQI guidelines in 1997. However, the K/DOQI clinical practice guideline recommending that an autologous fistula be placed in 40% of prevalent hemodialysis patients is not being met. The use of tunneled catheters as the primary means of hemodialysis access appears to be rising.[31] Considerable challenges remain in attempting to optimize vascular access practice patterns in the future.

Arteriovenous Fistula

Creation of a native vein fistula requires that an anastomosis be made between an adequate artery and vein in close proximity to each other. The most commonly used site is at the wrist, where the cephalic vein is connected to the radial artery (i.e., Brescia-Cimino fistula). The original operation described by Brescia and colleagues[19] was a side-to-side, artery-to-vein anastomosis. However, the end-to-side configuration is preferred by many surgeons today because there is a lower incidence of venous hypertension in the hand.[32] A radial-cephalic fistula can also be fashioned more distally in the anatomic snuff-box.[33] Although radial-cephalic fistulas are preferred when feasible, several reports suggest that, when an aggressive approach is undertaken, a high percentage of radial-cephalic fistulas fail to mature or develop thrombosis. Failure of radial-cephalic fistula maturation is especially prevalent in female, diabetic, and older hemodialysis patients. [34]

An alternative to the radial-cephalic fistula is to use the veins of the upper arm to create a brachiocephalic fistula or a brachiobasilic fistula. Because the basilic vein in the upper arm generally lies under deep fascia, use of this vein for an arteriovenous fistula requires that the vein be dissected and transposed into a more convenient subcutaneous position.[35] The brachial artery can also be anastomosed to a perforating vein, joining the superficial and deep venous system just below the elbow crease (i.e., Gracz fistula).[36] Compared with brachiocephalic fistulas, transposed brachiobasilic fistulas are more likely to mature, but have a higher long-term thrombosis rate.[37] Better patency for upper arm fistulas compared with lower arm fistulas or arteriovenous grafts has been reported, supporting the trend toward creation of upper arm arteriovenous fistulas as the access of choice in patients with poor forearm venous anatomy.[37] [38]

Several strategies are being used to increase the prevalence of functioning arteriovenous fistulas in the U.S. dialysis population.[39] It has been suggested that systematic use of preoperative ultrasonographic imaging can increase the success rate in the surgical placement of arteriovenous fistulas. [40] [41] Arterial and venous anatomy should be examined, and the cephalic vein should be examined from the wrist to the cephalic-subclavian junction. The vein should be at least 2.5 mm in diameter at the point of anastomosis to increase arteriovenous fistula success. Another successful strategy for increasing arteriovenous fistula prevalence involves ligation of tributary veins when arteriovenous fistulas fail to mature promptly. Surgical and endovascular techniques have been used. Whether the short-term use of antiplatelet agents after arteriovenous fistula creation can reduce early fistula thrombosis and increase the number of functioning arteriovenous fistulas is under study.

Arteriovenous Grafts

Dialysis arteriovenous grafts made of ePTFE continue to be the most frequently placed type of permanent dialysis access in the United States, accounting for up to 80% of all accesses, depending on geographical region. Compared with bovine carotid artery graft biomaterial, ePTFE grafts appear to have fewer complications and allow easier management of infection by a potential surgical excision of the infected graft segment. The ePTFE grafts have the advantage of low early thrombosis rate, surgical ease of placement, and a relatively short time between access creation and successful cannulation. However, short-term advantages are more than outweighed by the long-term increased risk for infection and thrombosis.[27] [42] Unfortunately, the 1- and 2-year primary patency rates for ePTFE grafts are a dismal 50% and 25%, respectively.[43] Graft thrombosis accounts for 80% of all vascular access dysfunction, and in more than 90% of thrombosed grafts, venous stenosis at or distal to the graft vein anastomosis is detected.[44] The underlying pathology for the development of venous stenosis is venous neointimal hyperplasia with exuberant vascular smooth muscle cell proliferation, neoangiogenesis within the neointima and adventitia, and an inflammatory macrophage cell layer lining the ePTFE graft material.[45] [46] Immunohistochemical studies have revealed the presence of vascular growth factors, cytokines, byproducts of oxidative stress, and inflammatory proteins within the intimal hyperplastic lesions obtained from hemodialysis patients.[46] [47] These studies suggest that specific pathophysiologic processes lead to venous stenoses in hemodialysis patients with arteriovenous grafts that may be amenable to pharmacologic inhibitory approaches.[48]

Vascular Access Monitoring and Surveillance

A significant advance in the care of hemodialysis patients with arteriovenous fistulas and grafts is the recognition that physiologic monitoring of access function can frequently identify incipient access failure before thrombosis. Vascular access monitoring is based on the premise that identification of high-risk patients for access thrombosis, coupled with elective correction of stenotic lesions, can decrease the incidence of vascular access failure and improve patient outcomes. Schwab and associates[49] initially demonstrated that intradialytic dynamic venous pressure monitoring of arteriovenous grafts had utility in the detection of graft-associated stenosis. Available hemodialysis vascular access monitoring techniques include physical examination,[50] static and dynamic venous pressure monitoring,[49] [51] vascular access blood flow monitoring,[52] [53] [54] [55] [56] [57] [58] [59] vascular access imaging,[60] [61] [62] and measurement of access recirculation. Implementation of comprehensive vascular access surveillance programs has achieved access thrombosis rates lower than those targeted by current clinical practice guidelines. In a nonrandomized study, instituting a vascular access blood flow monitoring program substantially decreased graft thrombosis rates and reduced the number of hospital days, missed outpatient dialysis treatments, and the use of dialysis catheters because of thrombotic events.[52] Although venous stenoses developed less frequently and at a slower rate in patients with native arteriovenous fistulas compared with arteriovenous grafts, it has been suggested that vascular access blood flow monitoring has utility in this patient population as well.[63] Although almost all available data suggest considerable utility for vascular access monitoring and surveillance, there are no published randomized trials comparing results of monitoring with no monitoring.

Treatment of Vascular Access Dysfunction

When an arteriovenous fistula or arteriovenous graft thromboses, thrombectomy must be performed, or a new dialysis access site must be created. Thrombectomy can be performed by endovascular or surgical techniques and must be accompanied by correction of the underlying pathophysiology leading to thrombosis (frequently a venous stenosis). When native arteriovenous fistulas thrombose early, technical factors are often responsible. Successful surgical revision has been reported in 14% to 90% of cases. Late thrombotic occlusion of autologous fistulas is usually due to outflow stenosis, and surgical approaches are less successful. Endovascular treatment of thrombosed autologous fistulas is generally reported to have a higher success rate than surgical techniques, but should not be attempted when there is suspected infection in the access. When arteriovenous grafts thrombose, similar success is reported with surgical and endovascular techniques. In all cases, attention must be directed to searching for and dilating or bypassing stenoses, including central venous lesions. Unfortunately, primary patency rates after graft thrombosis has occurred are dismal, generally in the range of 20% to 40% at 1 year.[79] [80] [81] [82]

The poor results for arteriovenous fistulas and grafts that occurred after thrombosis led to successful implementation of surveillance and monitoring strategies. Stenotic lesions detected can in most cases undergo prophylactic percutaneous transluminal angioplasty with surgical revision reserved for recurrent stenoses or for long stenoses not amenable to percutaneous techniques. Clinical practice guidelines strongly support the judicious use of angioplasty and stents to preserve access function. However, although this approach has been documented to result in an approximately twofold to threefold decrease in the incidence of access thrombosis, the primary patency rate for arteriovenous grafts after angioplasty is approximately 60% at 6 months and 40% at 12 months in the best studies.[80] [83] [84] [85] There are no randomized, controlled trials demonstrating further efficacy or reduced costs associated with this approach.

Pharmacologic Prevention of Vascular Access Failure

Given the high cost of morbidity associated with vascular access failure, effective pharmacologic prevention of vascular

access dysfunction and failure would likely have clinical utility and be cost-effective. [48] There are few randomized clinical trials of drug therapy to prevent hemodialysis vascular access dysfunction. Two separate pilot double-blind, randomized, prospective trials have suggested that fish oils or dipyridamole may be effective in reducing ePTFE graft thrombosis.[86] [87] A multicenter Veterans' Administration Cooperative Trial comparing a combination of clopidogrel plus aspirin versus placebo was discontinued prematurely due to an increase in bleeding complications in the active treatment group.[88] Several studies have suggested that short-term use of antiplatelet agents may reduce early thrombosis after native arteriovenous fistula placement. Retrospective analysis has suggested that the use of ACE inhibitors and calcium entry blockers may prolong survival of dialysis grafts.[89] [90] Because of the importance of this clinical and biologic problem, the National Institutes of Health developed a Dialysis Access Consortium, which is conducting multicenter, prospective, randomized, clinical trials of pharmacologic agents designed to reduce the vascular access failure rate for arteriovenous grafts and fistulas.

ARTIFICIAL PHYSIOLOGY: GENERAL PRINCIPLES OF HEMODIALYSIS

The differences between native and artificial kidneys are germane to this discussion. There are 1 to 2 million functioning elements or nephrons in the two native kidneys. The artificial kidney, in its hollow-fiber format, contains 8000 to 10,000 fibers and provides a surface area for exchange as high as 1.8 to 2 m2 . The proximal tubule of the nephron is 40 µm in diameter and is 14 mm long, and each hollow fiber is about 200 µm in diameter and more than 25 cm long. In addition to being influenced by diffusive and convective forces, the tubules perform a myriad of biochemical processes on the fluid that is filtered at the glomerulus whereas depuration in the artificial kidney is solely dependent on the physical forces of diffusion and convection across a semipermeable membrane.

Clearance

Definitions and Principles

The physiologist uses the concept of clearance to describe the net result of the transport functions of the kidney. The clearance of a substance is the amount removed from plasma, divided by the average plasma concentration over the time of measurement. Clearance is expressed in moles or weight of the substance per volume per time. It can be thought of as the volume of plasma that can be completely cleared of the substance in a unit of time. Clearance is also a useful concept when describing the process of dialysis.

The goals of dialysis are straightforward: to remove accumulated fluid and toxins. With respect to toxins, the goal is to maintain their concentrations below the levels at which they produce uremic symptoms. However, the toxic levels of retained substances are not used as performance measures for dialysis because their identities are unknown. Instead, performance of dialysis is judged by clearance. If the generation of a substance is fixed, its clearance (i.e., removal rate from plasma/plasma concentration) then becomes a measure of its concentration levels in the patient. The principles and the calculation of clearance are the same for all substances removed by dialysis.

Dialysis relies on the mass transfer across semipermeable membranes. The hemodialysis membranes separate the blood and dialysate compartments. Diffusion, convection, and ultrafiltration across the membrane are properties that are integral to the dialysis procedure. Diffusion describes the movement of solutes from one compartment to another, relying on a concentration gradient between the two compartments. This is the principal mechanism for toxin removal during hemodialysis. Convective transport involves the movement of solutes by bulk flow in association with fluid removal. Convective clearance is the mechanism of toxin removal by the depurative process known as hemofiltration. It is not dependent on concentration gradients and the magnitude of its contribution to clearance is directly related to the ultrafiltration rate. Mass solute removal across the dialyzer is a function of effective blood flow (QB ) and differences between the afferent and efferent concentrations of solute, traditionally labeled as "arterial" and "venous" (CA and CV ). The definition of diffusive dialyzer clearance (K), similar to creatinine clearance in the normal kidney, is calculated as:

K = (QB )(CA − CV )/CA

In the equation, (QB )(CA − CV ) represents the amount of solute removal and CA is the driving force. This formula describes diffusive clearance when single-pass hemodialysis circuits, in which the blood side is always in contact with fresh dialysate that is continuously being generated, are employed. Older systems employed discrete batches of dialysate that were recirculated. The result of these configurations is that concentrations of the removed toxins rise in the dialysate. The consequence is that the driving force to diffusion decreases. In this case, the driving force is described by CA − DI , in which DI is the concentration of the removed substance in the dialysate. Instead of clearance, the term dialysance is used:

D = (QB )(CA − CV )/(CA − DI ).

The efficiency of recirculated hemodialysis systems is inferior to single-pass systems because the driving force for diffusion is continuously being dissipated by the appearance in the dialysate of the substances being removed. Systems employing single-pass dialysate circuits are almost universally employed.

These equations, however, neglect the contribution of convection. This phenomenon is directly related to ultrafiltration and involves the bulk movement of fluid across dialyzer membranes. The driving force for ultrafiltration is the hydrostatic pressure gradient across the membrane, the transmembrane pressure (TMP). With ultrafiltration, blood flow leaving the dialyzer (QBo ) is less than blood flow entering the dialyzer (QBi ). The difference between these values represents ultrafiltration (Quf ). This can be incorporated into the previous equation to yield a more precise definition of clearance:

True clearance should be calculated by using the concentration in the aqueous compartment of blood and the concentration of solute in that compartment. Because solutes diffusing out of blood appear in the dialysate, it is possible to calculate clearance for solutes not present in the incoming dialysate (e.g., urea) as follows:

K = QDo (CDo )/CA

In this equation, CDo and QDo are the concentrations of solute in the dialysate outlet and the effluent dialysate flow, respectively. Although this equation provides a simple concept for determining clearance, the necessity of measuring low concentrations of any substance in the dialysate increases the error of measurement. The most accurate measurement of dialyzer clearance is achieved when "blood-side" and "dialysate-side" clearances are obtained, ensuring mass balance.

Factors Influencing Clearance

Several variables affect clearance by the dialyzer ( Table 59-2 ). The physical and chemical properties of the substance to be removed and its distribution in the body are toxin-related variables. The procedure-related variables include the permeability of the membrane to toxins of various sizes (flux), its hydraulic permeability, the membrane surface area, dialysis time, blood and dialysate flow rates and dialysate composition.

The size and charge of the molecule are important intrinsic physical features governing its removal. If the molecule is charged, its behavior is governed by the Donnan equilibrium. The cation concentration on the blood side of the membrane is higher because of the presence of plasma proteins that are negatively charged ( Fig. 59-5 ).

In the case of sodium, the dialysate-side concentration of sodium should be approximately 3 mEq/L less than the blood-side concentration to prevent net transfer of sodium from dialysate to the patient. The lower the molecular weight of the substance, the greater its rate of movement across the membrane or flux (J). Other factors such as binding of the toxin to plasma proteins, a large volume of distribution or delayed transfer of the substance from the intracellular pool to the intravascular space results in decreased clearance. An important example of the latter principle involves phosphorus. In Figure 59-6 , phosphorus

TABLE 59-2 -- Factors Influencing Clearance by the Dialyzer

PROCEDURE RELATED (IN ORDER OF IMPORTANCE)

TOXIN RELATED Low-Molecular-Weight Toxin High-Molecular-Weight Toxin

Size Dialysate composition * Flux

Charge Blood flow Time

Protein binding Dialysate flow Membrane surface area

Volume of distribution Membrane surface area Blood flow

Time Dialysate flow

Flux Dialysate composition *

*For potassium, calcium, sodium, and total CO2 , this factor is not applicable.

is rapidly removed from the intravascular compartment and the patients actually become hypophosphatemic during the hemodialysis treatment. However, there is a rebound in the postdialysis interval with phosphorus levels rapidly returning to predialysis levels. Although phosphorus is a relatively small molecule, hemodialysis alone is not sufficient to control its level.

As the molecular weight of the substance increases, the properties of the dialysis membrane become increasingly important factors with regard to clearance. The association of J with clearance of the toxin is given in the following formula:

J = A(ΔC/R)

In this equation, A is the surface area of the membrane in the dialyzer, ΔC is the concentration gradient between blood and dialysate, and R represents resistance to diffusivity of the substance across the membrane and the thickness of the membrane.

Removal of low-molecular-weight substances follows first-order kinetics. The efficiency of the removal of substances depends on the concentration of the toxin in the blood. Blood and dialysate flow rates are the most important variables for clearance of the small molecular substances. Clearance of higher-molecular-weight substances depends on membrane porosity, surface area, and dialysis time.

Figure 59-5 Consequences of the Donnan equilibrium.

Figure 59-6 Clearance as a function of dialyzer type.

To increase the clearance of low-molecular-weight substances, mere engineering issues must be addressed. Dialyzers with larger surface areas or hollow-fiber geometry that permit higher blood flows to be used without promoting turbulence can be constructed. Two large dialyzers can be connected in series or in parallel configurations to increase the clearance of low-molecular-weight toxins. High-efficiency dialysis can be accomplished in patients with low to average body surface areas (i.e., body surface area bears a direct relationship to the volume of distribution of substances such as urea or creatinine) without major increases in dialysis time. However, multiple lines of evidence are emerging that lengthening dialysis time leads to better blood pressure control, nutritional status, and phosphorus management. The rate at which fluid can be safely mobilized from the various body compartments without producing hemodynamic instability also places limits on how short the treatment can be. These issues are dealt with in subsequent sections.

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Now for the rest of you, Here's the ONTOPIC PART OF THIS POST!!!

[quote=Brenner & Rector's The Kidney, 7th ed., Copyright © 2004

Chapter 59 - Hemodialysis

Gerald Schulman

Jonathan Himmelfarb]

Hemorrhage

The uremic environment produces impaired platelet functioning, changes in capillary permeability, and anemia, all of which can impair hemostasis. There also may be increased blood loss from the gastrointestinal tract because of gastritis or angiodysplasia, lesions associated with renal failure.

The initiation of hemodialysis is reported to partially correct the defects responsible for the platelet dysfunction and capillary permeability that occur in uremia. However, patients undergoing hemodialysis still have a higher risk of hemorrhagic events because of repeated exposure to heparin. Heparin is used to prevent clotting in the extracorporeal circuit. Although strategies have been developed to dialyze patients without systemic anticoagulation, these techniques are time consuming and require greater supervision than is practical in the setting of an outpatient chronic hemodialysis center.

Acute bleeding episodes can occur at many sites; gastrointestinal blood loss, subdural and retroperitoneal hematomas, and the development of a hemopericardium may be life threatening. Patients with acute inflammatory pericarditis, those who have had trauma or who have had recent surgery, or who have an underlying coagulopathy or thrombocytopenia are at particular risk for developing hemorrhagic complications during hemodialysis.

In addition to acute bleeding episodes, patients undergoing hemodialysis are exposed to chronic, low-grade episodes of blood loss with each dialysis treatment. Between 5 and 10 mL of residual blood remains in the artificial kidney and tubing even after thorough rinsing. There may be blood loss as needles are inserted and removed and as repeated blood tests are performed on the patients. Estimates of loss of between 5 and 50 mL of blood per dialysis treatment have been made.

Prevention of bleeding episodes requires identification of patients who are at increased risk. In hospitalized patients, regional anticoagulation, a technique by which citrate isinfused as blood leaves the patient and calcium is infused as blood returns to the patient, permits anticoagulation of blood only when it is in the extracorporeal circuit. If the patient is closely supervised, the use of heparin-free dialysis may be useful. In this case, blood coagulation of the extracorporeal circuit is prevented by maintenance of high blood flows (>300 mL/minute) and frequent flushes of saline into the extracorporeal circuit. There is a suggestion that low hematocrit in itself predisposes to bleeding. The use of erythropoietin to increase hematocrit may lessen the risk of bleeding. Attention to iron stores and iron supplementation is therefore important in these patients. The use of low-molecular-weight heparin compounds should be avoided in patients with ESRD. Massive hemorrhage has been described with repeated use of these compounds in dialysis patients.

Abnormalities of Coagulation and Fibrinolysis

Activated partial thromboplastin, prothrombin, and thrombin times are generally normal in uremia[223] [264] [265] [266] [267] [268] [269] [270] [271] [272] ; fibrinogen and factor VIII:C are usually increased. Changes in the major natural inhibitors of coagulation have been found. Conflicting results regarding antithrombin III levels have been reported; in fact, previous reports demonstrated increased levels of this natural anticoagulant.[264] [273] [274] [275] Reduced levels of antithrombin III have been found in uremic patients.[276] [277] This evidence, together with the observed decrease in protein C anticoagulant activity with normal protein C amidolytic activity and antigen[278] [279] and decreased protein S,[280] may further contribute to the thrombotic tendency. Thrombin is continuously formed, as demonstrated by increased levels of the thrombin-antithrombin III complex,[211] [281] [282] [283] D dimer,[277] [281] [282] [284] and fibrinopeptide A.[281] [282] [285] [286] These findings suggest that a hypercoagulable state exists in chronic uremia. Contrasting results regarding the fibrinolytic system have been obtained. Previous reports described decreased fibrinolytic activity in uremia either absolutely[285] [287] [288] [289] [290] [291] [292] or relative to the extent of activation of coagulation,[275] and this has been used as an explanation for the thrombotic tendency. Studies found, instead, activation of fibrinolysis in uremia, with an increase of plasmin-antiplasmin complexes[211] [284] [283] and fibrinogen and fibrin degradation products [211] [277] [281] as well as a decrease in the activity of plasminogen activator inhibitor in ESRD [201] and after HD sessions.[283] [294] These findings probably reflect a fibrinolytic response secondary to fibrin deposition, which may take place also if the overall fibrinolytic activity is depressed. These abnormalities of coagulation or fibrinolysis partially corrected by dialysis[287] [295] predispose the uremic patient to thrombosis rather than bleeding. Of interest, levels of protein C and its cofactor protein S are further and significantly decreased in association with EPO therapy, a finding that may contribute to the

Thrombotic Complications

Thrombosis of the arteriovenous shunt is a frequent occurrence in uremic patients undergoing HD. Plasma levels of lipoprotein(a), an independent risk factor for atherosclerotic cardiovascular disease, are markedly increased in chronic uremic patients either on HD[296] [297] or CAPD.[297] Because platelet aggregation plays a major role in thrombus formation, antiplatelet agents have been used, with encouraging results. Sulfinpyrazone, aspirin, or dipyridamole, singly or in combination, have proved useful in several studies.[298] Fibrinolytic agents, such as streptokinase[299] [300] or urokinase,[301] have produced contrasting results. More studies are needed to determine the most effective treatment for this complication.

Therapeutic Strategies

Although some investigators have found that both HD and PD partially improve the hemostatic abnormality of uremia, both forms of dialysis can potentially produce adverse effects on hemostasis ( Table 49-3 ). For all patients with hemorrhagic complications or undergoing major surgery, the adequency of dialysis should be appropriately checked. It is also advisable to change the dialysis schedule for 1 or 2 months in patients who have experienced severe hemorrhages (such as major gastrointestinal bleeding, hemorrhagic pericarditis, subdural hematomas) or who have undergone recent cardiovascular surgery so that heparin can be avoided. Acute bleeding episodes may be treated with desmopressin at a dose of 0.3 µg/kg intravenously (added to 50 mL of saline over 30 minutes) or subcutaneously. Intranasal administration of this drug at a dose of 3 µg/kg is also effective and is well tolerated. The effect of desmopressin lasts only a few hours, a major limitation to its use in treating severe hemorrhage, and desmopressin appears to lose efficacy when repeatedly administered. Because the favorable effect of cryoprecipitate on bleeding time has not been uniformly observed, we do not recommend its use. The ideal treatment of persistent chronic bleeding should have a

TABLE 49-3 -- Guidelines for the Management of Hemorragic Complications of Uremia For patients with hemorragic complications or undergoing major surgery, dialysis adequacy should be assessed.

Acute anemia should be promptly corrected and hematocrit should be increased to 30% or more, by infusion of packed red blood cells. For long-term correction of anemia, erythropoietin is administered.

Acute bleeding episodes may be treated by intravenous infusion of desmopressin at a dose of 0.3 µg/kg body weight in 50 mL of saline over 30 min, or by subcutaneous injection at the same dose. Intranasal administration of desmopressin at a dose of 3 µg/kg body weight is also effective. The effect of desmopressin is short-lasting, and repeated doses are associated with loss of effect.

Persistent chronic bleeding may be effectively treated with intravenous infusion of conjugated estrogen. The usual dose schedule is 0.6 mg/kg body weight per day for 5 days.

long-lasting effect. Conjugated estrogen treatment given by intravenous infusion in a cumulative dose of 3 mg/kg as daily divided doses (e.g., 0.6 mg/kg for 5 consecutive days) is the most appropriate way of achieving long-lasting hemostatic competence. Severely anemic patients should receive blood or RBC transfusions to improve hematocrit values. RBC transfusions are hemostatically effective only when the hematocrit rises above 30%. As an alternative, bleeding in patients with renal failure and hematocrit less than 30% can be treated successfully with erythropoietin (see Table 49-1 ).

PD has been reported to cause platelet hyperreactivity, which in some cases may be related to hypoalbuminemia.[302] HD is accompanied by a transient form of platelet activation related to the interaction of platelets with artificial membranes[303] [304] [305] [306] [307] [308] [309] [310] and vascular access itself.[311] [312] Dialysis patients have an accelerated platelet turnover,[313] supporting the concept that platelets are chronically activated by dialytic treatment. Repeated platelet activation on dialysis membranes may induce refractoriness to further platelet stimulation, possibly contributing to clinical bleeding that can occur at termination of the dialysis procedure. It has been documented that plasma levels of the potent NO inducers TNF-α and IL-1β rise during dialysis. IL-1 and TNF are generated in vivo by circulating monocytes during HD with complement-activating membranes.[195] [196] [197] [198] Production of increased cytokines may also be triggered by intact endotoxin, endotoxin fragments, and other bacterial toxins that may cross the dialysis membranes,[312] [313] [314] and also by acetate-containing dialysate.[206] [207] [208] [314] [315] [316] [317] As a result of massive release of cytokines during dialysis, there is an increase in NO synthesis ( Fig. 49-4 ). Yokokawa and associates[318] found that uremic patients may occasionally have an increase in plasma levels of NO metabolites during HD. In addition, in a study it was found that plasma collected after HD appears to stimulate NO synthesis by cultured endothelial cells more than does plasma from the same patients before dialysis.[319] Thus, the capacity of the dialysis procedure to remove uremic toxins is negatively counterbalanced by its effects on platelet activation and NO synthesis.

In addition, heparin may also present a problem. "Regional" heparinization has been used to minimize the effects of systemic anticoagulation.[320] [321] [322] Heparin is given by constant infusion through the inlet line of the dialyzer. Simultaneously, protamine sulfate is infused into the outlet port before the blood returns to the patient. Even this schedule of heparin administration, however, may be associated with a high incidence of bleeding.[323] As an alternative, frequent injections of low-dose heparin can be given during dialysis to maintain a lower and more constant level.[324] Usually, 40 to 50 IU/kg of heparin is given at the beginning of HD, followed by 60% of the initial dose after 1 hour and 2 hours, and 30% of the initial dose after 3 hours. [314] The activated partial thromboplastin time (APTT) is measured hourly and should be maintained at 1.5 to 2.0 times the basal value. Patients at high risk for bleeding can use an ethylene-vinyl alcohol copolymer hollow-fiber dialysis membrane that does not require systemic anticoagulation, provided that blood flow is maintained at more than 200 mL/minute.[325] Low-molecular-weight heparin has been proposed as an alternative to unfractionated heparin in patients receiving chronic HD who are at high risk for bleeding.[326] Dermatan sulfate has been proposed[327] as an alternative to heparin, because it causes less

Figure 49-4 Proposed mechanism for NO-mediated disorders in uremia. The contact with dialysis membrane or acetate dialysis buffer activates circulating monocytes that release cytokines, such as tumor necrosis factor-α (TNF-α). TNF-α causes the transcription of inducible NO synthase messenger RNA in vascular endothelial cells that release a large amount of NO either in the circulation or within the vessel wall. NO enters target cells (platelets and smooth muscle cells), where it activates soluble guanylate cyclase, causing impairment of platelet function (hence bleeding tendency) and relaxation of smooth muscle cells (hence vasodilation).

bleeding than heparin in animal models. This may be due to its reduced effect on platelets.[328] [329] It also induced a moderate prolongation of APTT.[328] [330] [331] Effective doses ranged from 6 to 10 mg/kg body weight per dialysis session, depending on the type of dialyzer and the duration of the procedure.[328] [330] [331] [332] [333] [334] The dermatan sulfate dose can be given as a single predialysis bolus when the procedure is of short duration (4 hours); when the dialysis lasts for a longer period, a combined regimen (bolus plus infusion) is required. A comparative short-term clinical study has been performed on 10 hemodialyzed patients,[334] demonstrating that the DS dose can be individually titrated to suppress clot formation during HD as efficiently as does individualized heparin. Aspirin and dipyridamole analogs reduce fibrin and cellular deposition on the filter membrane but increase the risk of gastrointestinal bleeding.[261] [335] Prostacyclin shows some promise as an alternative.[336] [337] [338] Given in a continuous infusion during dialysis at a mean dose of 5 ng/kg/minute, prostacyclin completely inhibited platelet aggregation without causing bleeding.[326] However, it was associated with headache, flushing, tachycardia, and chest and abdominal pain, which required careful monitoring and a physician's supervision.[338] [339] [340] Thus, the use of prostacyclin should be limited to patients at high risk for hemorrhage. PD, when applicable, avoids the risk of bleeding associated with heparin or anticoagulants. Anemia can contribute to the prolongation of bleeding time in uremia.[233] [234] [235] The progressive increase in hematocrit associated with rhEPO therapy was accompanied by a significant decrease in the bleeding time ( Fig. 49-5A ).[237] [238] [341] No consistent changes were found in platelet number, platelet aggregability, or platelet TXA2 formation.[227] [341] Several studies[342] [343] [344] observed a significant increase in the levels of vWF and ristocetin cofactor activity. In a study, 20 dialysis patients with prolonged bleeding time (average: 15 minutes) were randomly allocated to rhEPO or no specific treatment. EPO was given intravenously at the dose of 50 IU/kg three times a week; every 4 weeks the dose was increased by 25 IU/kg until bleeding time became normal. An EPO dosage of 150 to 300 IU/kg/week increased PCV to

Figure 49-5 A, Correlation between bleeding time and packed cell volume in patients treated with erythropoietin. B, Effect of rhEPO therapy on packed cell volume and bleeding time in uremic patients. Dotted area indicates the threshold of packed cell volume to be reached for normalization of bleeding time values. (From ViganÒ G, Benigni A, Mendogni D, et al: Recombinant human erythropoietin to correct uremic bleeding. Am J Kidney Dis 18:44–49, 1991.)

a range of 27% to 32% and normalized bleeding times in all patients (see Fig. 49-5B ). A significant negative correlation was found between PCV and bleeding time.[238] Thus, the correction of anemia with rhEPO may contribute significantly to the prevention and control of bleeding in uremic patients.

Cryoprecipitate is a plasma derivative rich in vWF, fibrinogen, and fibronectin that has traditionally been used in the treatment of hemophilia A, von Willebrand disease, hypofibrinogenemia, and dysfibrinogenemia. Cryoprecipitate corrects prolonged bleeding in uremic patients within 4 to 12 hours, and the effect lasts 24 to 36 hours.[237] The mechanism of action of cryoprecipitate is not known. A small rise in platelet levels of fibrinogen and vWF-related proteins were the only changes noted after cryoprecipitate infusion. Different preparations of cryoprecipitate, however, had different effects on bleeding time.[345] The poor reproducibility of results and the risk of disease transmission prompted the search for alternatives to cryoprecipitate.

Desmopressin (1-deamino-8-D-arginine-vasopressin)—a synthetic derivative of antidiuretic hormone—induces the release of autologous vWF from storage sites.[346] In a randomized, double-blind, crossover trial, desmopressin given intravenously at a dose of 0.3 mg/kg body weight in 50 mL of physiologic saline over a period of 30 minutes temporarily corrected the prolonged bleeding time in patients wi