At the ASAIO Meeting in 1982, Peter Kramer, from Göttingen, Germany, presented a paper describing the use of arteriovenous hemofiltration in the management of acute renal failure (ARF).1 He described his experience of attaching a microporous hemofilter to the femoral artery and vein, and flowing blood through it at around 100 ml/min. Liters of plasma filtrate (extracellular fluid) poured out. He replaced it with an infusion of electrolyte solution, which did not contain urea, creatinine, potassium, or other molecules normally cleared by the kidney. He explained that this could be done continuously, avoiding the volume shifts and other problems of intermittent hemodialysis. For those in the audience who cared for patients with anuric ARF, this was an epiphany of thunderbolt proportions.
At that time, ARF in critically ill, multiple organ failure patients was managed by intermittent hemodialysis and the mortality rate was very high.2 Dialysis could control urea, potassium, and other toxic metabolites and could partially control extracellular volume. But dialysis had deleterious effects including increased metabolic rate, hypotension, and hemodynamic instability.3 Some of this was related to the acute volume shifts and many patients actually gained fluid at the end of a 6-hour dialysis run. We later learned that the cellophane membranes in use at the time stimulated an inflammatory response and myocardial dysfunction similar to endotoxin infusion. Because of this, we tried to use dialysis as sparingly as possible. The indications for dialysis in ARF were blood urea nitrogen in the 100s of mg%, stupor, or uremic frost. Feeding protein to patients in ARF generated urea, which required dialysis, so protein feeding was minimized. If protein was used at all, it was in the form of essential amino acids thinking that these would be anabolized rather than broken down.4
In the surgical intensive care unit (ICU) at the University of Michigan, we had been studying metabolism and nutrition in critically ill patients.5 We demonstrated that starvation was a major cause of mortality in critical illness,6 and demonstrated improved survival with full nutrition.7 In the course of those studies, we discovered that hemodialysis caused an acute increase in metabolic rate resulting in hemodynamic instability.3 We showed that starvation was a factor contributing to mortality in ARF.7
When we heard Peter Kramer presented that paper, we realized that it would be possible to feed patients in ARF without limit. We attached a hemofilter to the Scribner shunt in a patient in ARF, and out came liters of extracellular fluid! We quickly learned to control the output to 600 ml an hour and replaced it with 500 ml of isotonic salt solution supplemented with bicarbonate. It is difficult for modern intensivists and nephrologists to imagine the joy that occurred when watching the first continuous hemofiltration. Until that time, we had spent hours and days watching pitiful drops of urine collect in a drainage bag. We would “milk” the Foley catheter in a vain attempt to get a few more precious ccs of urine. We gave huge quantities of loop diuretics to whip the last few functional nephrons into action. We jealously limited every milliliter of intake to avoid volume overload. We cleared excess salt water with peritoneal dialysis or sorbitol enemas. We gave glucose and insulin to lower a dangerous potassium. If all else failed, we used hemodialysis, often giving more salt water than we removed during dialysis to maintain hemodynamic stability. I must admit that I wept with joy the first time seeing all that yellow fluid pouring out. It was not only good for my patient, it was the realization that all the problems of hemodialysis could be eliminated and we could feed patients in ARF without limit. Kramer was right. I mailed him immediately (airmail to Germany!).
Kramer et al.8 had actually first reported the use of continuous hemofiltration in Germany in 1977. Others, including Henderson et al.9 and Knopp,10 had studied hemofiltration in animals and as an alternative to dialysis in chronic renal failure, but it was really Peter Kramer’s report to ASAIO that stimulated many of us to undertake the serious evaluation of continuous arteriovenous hemofiltration (CAVH) in ARF in the ICU (Figure 1).
Others who heard Peter’s presentation did the same; Emil Paganini at Cleveland Clinic, Juan Bosch at Washington, Bob Geronemus in Florida, Claudio Ronco in Vicenza Italy, and Andre Kaplan in Connecticut were among those who realized the great potential of continuous hemofiltration. All of us can remember that magic moment when we saw yellow fluid pouring out and imagined the potential. We all set out to establish protocols, make replacement fluid, develop methods to measure continuous filtrate output, and collect filtrate at 10 L at a time. Nurses got a lot of exercise hanging liter bags of fluid, but they loved it because they could see the miraculous effects of continuous hemofiltration (Figure 2).
Over the next 4 years, CAVH was developed in several centers for managing ARF in critically ill patients with multiple organ failure. In 1984, we demonstrated that nutrition in ARF was possible with CAVH.11 In 1986, we reported improved survival from 9% to 38% with full nutrition in ARF, facilitated by CAVH.12 The early enthusiasts of CAVH held symposiums in Ann Arbor in 1984, Cleveland in 1985, and Florida in 1986. A workshop summarizing the development and role of continuous hemofiltration was presented at ASAIO in 1988.13
Over the next 30 years, continuous renal replacement therapy (CRRT) has been studied extensively. The technology and terminology were expanded to include slow continuous ultrafiltration for fluid removal without replacement, continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration. In 1986, the term continuous renal replacement therapy was applied to all these continuous approaches.14 Continuous renal replacement therapy has become the mainstay of management of renal failure for multiple organ failure patients in the ICU. (Intermittent hemodialysis is usually used for isolated renal failure.) Veno-venous access replaced arterial access. Companies now manufacture machines that accomplish all of the modes of CRRT nearly automatically (much easier for the nurses). The mortality of ARF is now 40–50%.15,16
Peter Kramer was a bright, enthusiastic innovator in artificial organs (Figure 3). Sadly, he died unexpectedly in 1984. But all of us who manage patients in ARF, and thousands of our patients, are ever indebted to him for his remarkable contribution.
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