Cancer chemotherapy administered via hemodialysis fistulas
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《血管的通路杂志》
1.Division of Oncology, West Penn Allegheny Health System, Allegheny General Hospital, Pittsburgh, Pennsylvania - USA
2.Division of Nephrology and Hypertension, West Penn Allegheny Health System, Allegheny General Hospital, Pittsburgh, Pennsylvania - USA
ABSTRACT
End-stage renal failure (ESRF) patients can develop cancer before or after kidney disease occurs. Cancer chemotherapy often needs to be administered via the sort of central venous catheter that is normally avoided in ESRF care. Three cases are presented in which ESRF patients received chemotherapy for cancer via existing
hemodialysis fistulas, and the consequences of central venous access in a fourth patient are discussed.
Key Words: Hemodialysis, Arteriovenous fistula, Cancer, Chemotherapy
INTRODUCTION
Renal failure confers no protection from malignancy. As survival times on chronic dialysis increase, more patients may have both cancer and renal failure. Chemotherapy regimens can be modified for dialysis patients, but create an expanded need for venous access. The infectious, thrombotic, and hemorrhagic risks of central catheters have been extensively described in the oncology (1) and renal failure populations (2, 3), each of which have characteristic coagulation disorders and immune defects. Fistulas are specialized structures designed to provide durable bidirectional venous access for hemodialysis. While fistulas are traditionally reserved for this purpose alone, their anatomic features are favorable for other types of vascular access. We present three cases in which cancer chemotherapy was
successfully delivered via dialysis fistulas, and a fourth case that illustrates the hazards of traditional venous access.
Case 1
A 55 year old woman was diagnosed with metastatic bladder carcinoma four years after removal of a grade 3-4 papillary transitional cell tumor by radical
cystectomy. Irreversible renal failure due to Goodpasture Syndrome occurred 5 months after surgery (4). An autogenous left brachiocephalic fistula provided reliable access for hemodialysis. Metastases were found in the iliac lymph nodes and the liver. When chemotherapy was prescribed, the fistula was recruited for vascular access at the request of the patient and the nephrologist, both of whom were reluctant to incur the infectious risks of a central venous catheter. A cyclical regimen of cisplatinum and gemcitabine was administered via 23 gauge butterfly needles, which were inserted and removed by dialysis center staff. Hemodialysis was performed via 15 gauge fistula needles 6 hours after administration of gemcitabine to remove toxic metabolites (5). On one occasion, a chemotherapy needle was removed and replaced due to minor subcutaneous infiltration, which resulted in a nontender ecchymosis of approximately 0.5 cm diameter. Otherwise, chemotherapy was tolerated well. Kt/V results ranged from 1.75-1.98 during 210 minute treatments, which did not change after chemotherapy began.
Case 2
A 70 year old woman started hemodialysis for kidney failure due to
longstanding diabetes. A goretex graft had been inserted expectantly, and was sustained with intermittent percutaneous interventions. Small cell carcinoma of the lung was diagnosed 6 years later, and 6 cycles of carboplatin and taxol were administered over 4 months via peripheral
venipunctures. Brain metastases developed, and advanced despite irradiation. Peripheral venous access could not be achieved. Navelbine was administered weekly nine times via 15 gauge fistula needles at the conclusion
of dialysis treatments. Urea kinetics showed a stable Kt/V from 1.68-1.85, on 240 minute treatments. Despite a partial response to chemotherapy, she died
of a cerebrovascular accident 4 months later.
Case 3
A 54 year old woman with a 28 year history of ESRF due to polycystic kidney disease presented with colon cancer. Her second cadaver renal transplant
was deteriorating slowly due to chronic allograft nephropathy, and a right brachiocephalic fistula had been placed in anticipation of hemodialysis.
Peripheral venous access was not otherwise achievable. She received 18 weekly doses of adjuvant chemotherapy with 5-fluorouracil (5FU) and leucovorin via 23 gauge butterfly needles inserted in the fistula. Pulmonary metastases developed 18 months after diagnosis. The fistula was accessed approximately 80 times to administer multiple cycles of chemotherapy, including oxaliplatin, irinotecan, 5FU, and leucovorin. The fistula was also accessed repeatedly with 20-23 gauge butterfly needles for blood sampling and supportive therapy. She received infusions of calcium, magnesium, atropine, antiemetics and blood products via the fistula, which remained intact. Death due to metastatic disease occurred prior to recurrent ESRF.
Case 4
A 76 year old man presented with 3 months of hematochezia, 4 years after starting hemodialysis. An incidental T2N0M0 esophageal carcinoma was
found during endoscopy. Surgical resection was deemed impractical due to advanced cardiomyopathy, and he was referred for 3-dimensional conformal
radiotherapy. Intravenous carboplatin and taxol were administered as a radiosensitizing agent via a central venous catheter.
He developed febrile neutropenia with negative blood cultures 5 weeks into therapy. Despite restoration of blood counts with G-CSF, he presented
with high fevers 10 days later. Methicillin sensitive staphylococcus (MSSA) was detected in blood cultures, and the vascular access catheter was removed.
Blood cultures were persistently positive for MSSA despite 4 weeks of intravenous vancomycin and gentamicin. Subsequent therapy with intravenous
oxacillin required 6 weeks of confinement to a nursing home and insertion of a peripherally inserted central catheter.
DISCUSSION
Arteriovenous fistulas, with or without interposition of synthetic conduits, are designed to meet the unique vascular access needs of hemodialysis patients. The 600-1200 mL/min blood flow through an unobstructed mature fistula provides the 400-500 mL/min required to permit adequate solute clearance
within a practical time period(6). Maturation of a fistula into a tough and durable structure occurs due to exposure of the venous circulation to pulsatile
high-pressure arterial blood flow. A working fistula is cannulated more than 300 times each year, and some fistulas remain in service for decades. Fistula blood flow is unidirectional from the arterial to the venous limb. Backwards flow does not occur. Although anatomically accessible from the periphery,
fistulas have much in common with central veins. Luminal diameter is much larger than a peripheral vein, and there is rapid washout of the fistula contents. Thickening and 慳rterialization?of vessel walls results in a non-fragile structure with reduced sensitivity to hypertonic or intrinsically irritating agents. Many dialysis patients have depleted peripheral veins and little vascular access aside from their fistulas. Within a hemodialysis program, it is typical to administer many types of medication via fistulas (Tab. I).
Blood products of every variety are commonly given via fistulas during hemodialysis treatments, and emergency cardiopulmonary resuscitation that occurs during hemodialysis is normally treated with agents given via the fistula. Initiatives to promote dialysis fistulas encourage strict limitation of peripheral venipuncture (7). Using a durable fistula for an irritating intravenous agent may be preferable to squandering scarce peripheral veins.
Fistulas differ from central venous catheters in important ways. An autogenous fistula presents little infectious risk to its owner. The sterile bloodstream and the non-sterile world are not persistently connected
by a foreign body. Autogenous fistulas are quite resistant to spontaneous thrombosis. While arteriovenous grafts are less resistant, thromboses
are frequently amenable to percutaneous salvage. In contrast to a central catheter, a fistula cannot fall out of its owner. Needle sites are normally located in peripheral positions where bleeding is relatively easy to control with direct pressure. Fistula blood flow is less profuse than in the superior vena cava, and the peripheral puncture site in a fistula is of smaller diameter than the less compressible puncture site of a central catheter. The pressure inside a fistula is normally one-half of the mean arterial pressure, which is higher than the pressure inside a central vein, but substantially lower than systolic arterial pressure. Thrombocytopenia and leukopenia impact more significantly upon the risks of central venous catheters than of fistulas. With these distinctions in mind, a hemodialysis fistula emerges as a reasonable alternative to either peripheral or central venous access for chemotherapy.
Case 4 illustrates the risks of central venous catheter access in hemodialysis patients. Approximately 1 in 55 patients with central venous hemodialysis
catheters will die of infectious endocarditis (3). This patient likely had endocarditis, although transesophageal echocardiography was not performed due to esophageal irradiation. The morbidity of this infection, as well as the invasive procedures and loss of liberty required for cure, would all have been avoided if the existing fistula had been accessed for chemotherapy.
We encountered intermittent episodes of emotional resistance to fistula use among health care personnel, some of which were surprisingly intense.
This reluctance arose in part from the traditionally vociferous protection of fistulas by nephrology teams. Staff nurses emphatically trained never to
touch a fistula arm for a needlestick or a blood pressure reading were understandably concerned about using a fistula for infusion of chemotherapy.
Nephrology personnel, comfortable with fistula use and accustomed to administering multiple intravenous agents during dialyses, needed to provide
close support. Concerns were expressed about the possibility of profuse hemorrhage, skin damage due to irritants, damage to the fistula, intra-arterial administration of drugs, and potential liabilities.
Aside from one minor cutaneous ecchymosis, none of these adverse events occurred. These results cannot be generalized to all hemodialysis patients. Success may have been predicated upon all three patients having congstanding reliable fistulas. Chemotherapy access could have been far more problematic if underdeveloped or unreliable fistulas were recruited. Assessment of fistula suitability by trained renal personnel is necessary,
as is meticulous training of everyone expected to participate in use of the access site. Our findings cannot be generalized to all chemotherapeutic
agents, some of which are more potentially irritating than others.
In conclusion, we present 3 cases in which cancer chemotherapy was successfully administered via a pre-existing mature hemodialysis fistula. No infusion-related injuries occurred. No detectable decreases in solute clearance were detected, nor any damage to any of the fistulas. Catheter-related bacteremia was avoided, and venous access was not depleted.
No procedures were needed to install, replace, or remove central catheters. For selected hemodialysis patients with malignancies, the dialysis fistula is a safe alternative chemoaccess site with unique anatomic advantages over peripheral veins or central venous catheters.
REFERENCES
1. Kuter DJ. Thrombotic complications of central venous catheters in cancer patients. Oncologist 2004; 9: 207-16.
2. Naumovic RT, Jovanovic DB, Djukanovic LJ. Temporary vascular catheters for hemodialysis: a 3-year prospective study. Int J Artif Organs 2004; 27: 848-54.
3. Sandroni S, McGill R, Brouwer D. Hemodialysis catheter-associated endocarditis: clinical features, risks, and costs. Semin Dial 2003; 16: 263-5.
4. Blas A 3rd, McGill R, Sandroni S. Case 4-2002: Cancer-associated obstruction and glomerular damage. N Engl J Med 2002; 346: 1751-2.
5. Kiani A, Kohne CH, Franz T, et al. Pharmacokinetics of gemcitabine in patients with end-stage renal disease: effective clearance of its main metabolite by standard hemodialysis treatment. Cancer Chemother Pharmacol 2003; 51: 266-70.
6. Krpan D, Demarin V, Prot F, Milutinovic S, Molnar V, Milutnovic E. Measurement of blood flow through AV-fistulas by means of Doppler sonography in regularly haemodialysed patients. Int J Artif Organs 1991; 14: 78-82.
7. McGill RL, Marcus RJ, Healy DA, Brouwer DJ, Smith BC, Sandroni SE. AV fistula rates: changing the culture of vascular access. The Journal of Vascular Access 2005; 6: 13-7.(J. Harney , S. Ahmed1, K.)
2.Division of Nephrology and Hypertension, West Penn Allegheny Health System, Allegheny General Hospital, Pittsburgh, Pennsylvania - USA
ABSTRACT
End-stage renal failure (ESRF) patients can develop cancer before or after kidney disease occurs. Cancer chemotherapy often needs to be administered via the sort of central venous catheter that is normally avoided in ESRF care. Three cases are presented in which ESRF patients received chemotherapy for cancer via existing
hemodialysis fistulas, and the consequences of central venous access in a fourth patient are discussed.
Key Words: Hemodialysis, Arteriovenous fistula, Cancer, Chemotherapy
INTRODUCTION
Renal failure confers no protection from malignancy. As survival times on chronic dialysis increase, more patients may have both cancer and renal failure. Chemotherapy regimens can be modified for dialysis patients, but create an expanded need for venous access. The infectious, thrombotic, and hemorrhagic risks of central catheters have been extensively described in the oncology (1) and renal failure populations (2, 3), each of which have characteristic coagulation disorders and immune defects. Fistulas are specialized structures designed to provide durable bidirectional venous access for hemodialysis. While fistulas are traditionally reserved for this purpose alone, their anatomic features are favorable for other types of vascular access. We present three cases in which cancer chemotherapy was
successfully delivered via dialysis fistulas, and a fourth case that illustrates the hazards of traditional venous access.
Case 1
A 55 year old woman was diagnosed with metastatic bladder carcinoma four years after removal of a grade 3-4 papillary transitional cell tumor by radical
cystectomy. Irreversible renal failure due to Goodpasture Syndrome occurred 5 months after surgery (4). An autogenous left brachiocephalic fistula provided reliable access for hemodialysis. Metastases were found in the iliac lymph nodes and the liver. When chemotherapy was prescribed, the fistula was recruited for vascular access at the request of the patient and the nephrologist, both of whom were reluctant to incur the infectious risks of a central venous catheter. A cyclical regimen of cisplatinum and gemcitabine was administered via 23 gauge butterfly needles, which were inserted and removed by dialysis center staff. Hemodialysis was performed via 15 gauge fistula needles 6 hours after administration of gemcitabine to remove toxic metabolites (5). On one occasion, a chemotherapy needle was removed and replaced due to minor subcutaneous infiltration, which resulted in a nontender ecchymosis of approximately 0.5 cm diameter. Otherwise, chemotherapy was tolerated well. Kt/V results ranged from 1.75-1.98 during 210 minute treatments, which did not change after chemotherapy began.
Case 2
A 70 year old woman started hemodialysis for kidney failure due to
longstanding diabetes. A goretex graft had been inserted expectantly, and was sustained with intermittent percutaneous interventions. Small cell carcinoma of the lung was diagnosed 6 years later, and 6 cycles of carboplatin and taxol were administered over 4 months via peripheral
venipunctures. Brain metastases developed, and advanced despite irradiation. Peripheral venous access could not be achieved. Navelbine was administered weekly nine times via 15 gauge fistula needles at the conclusion
of dialysis treatments. Urea kinetics showed a stable Kt/V from 1.68-1.85, on 240 minute treatments. Despite a partial response to chemotherapy, she died
of a cerebrovascular accident 4 months later.
Case 3
A 54 year old woman with a 28 year history of ESRF due to polycystic kidney disease presented with colon cancer. Her second cadaver renal transplant
was deteriorating slowly due to chronic allograft nephropathy, and a right brachiocephalic fistula had been placed in anticipation of hemodialysis.
Peripheral venous access was not otherwise achievable. She received 18 weekly doses of adjuvant chemotherapy with 5-fluorouracil (5FU) and leucovorin via 23 gauge butterfly needles inserted in the fistula. Pulmonary metastases developed 18 months after diagnosis. The fistula was accessed approximately 80 times to administer multiple cycles of chemotherapy, including oxaliplatin, irinotecan, 5FU, and leucovorin. The fistula was also accessed repeatedly with 20-23 gauge butterfly needles for blood sampling and supportive therapy. She received infusions of calcium, magnesium, atropine, antiemetics and blood products via the fistula, which remained intact. Death due to metastatic disease occurred prior to recurrent ESRF.
Case 4
A 76 year old man presented with 3 months of hematochezia, 4 years after starting hemodialysis. An incidental T2N0M0 esophageal carcinoma was
found during endoscopy. Surgical resection was deemed impractical due to advanced cardiomyopathy, and he was referred for 3-dimensional conformal
radiotherapy. Intravenous carboplatin and taxol were administered as a radiosensitizing agent via a central venous catheter.
He developed febrile neutropenia with negative blood cultures 5 weeks into therapy. Despite restoration of blood counts with G-CSF, he presented
with high fevers 10 days later. Methicillin sensitive staphylococcus (MSSA) was detected in blood cultures, and the vascular access catheter was removed.
Blood cultures were persistently positive for MSSA despite 4 weeks of intravenous vancomycin and gentamicin. Subsequent therapy with intravenous
oxacillin required 6 weeks of confinement to a nursing home and insertion of a peripherally inserted central catheter.
DISCUSSION
Arteriovenous fistulas, with or without interposition of synthetic conduits, are designed to meet the unique vascular access needs of hemodialysis patients. The 600-1200 mL/min blood flow through an unobstructed mature fistula provides the 400-500 mL/min required to permit adequate solute clearance
within a practical time period(6). Maturation of a fistula into a tough and durable structure occurs due to exposure of the venous circulation to pulsatile
high-pressure arterial blood flow. A working fistula is cannulated more than 300 times each year, and some fistulas remain in service for decades. Fistula blood flow is unidirectional from the arterial to the venous limb. Backwards flow does not occur. Although anatomically accessible from the periphery,
fistulas have much in common with central veins. Luminal diameter is much larger than a peripheral vein, and there is rapid washout of the fistula contents. Thickening and 慳rterialization?of vessel walls results in a non-fragile structure with reduced sensitivity to hypertonic or intrinsically irritating agents. Many dialysis patients have depleted peripheral veins and little vascular access aside from their fistulas. Within a hemodialysis program, it is typical to administer many types of medication via fistulas (Tab. I).
Blood products of every variety are commonly given via fistulas during hemodialysis treatments, and emergency cardiopulmonary resuscitation that occurs during hemodialysis is normally treated with agents given via the fistula. Initiatives to promote dialysis fistulas encourage strict limitation of peripheral venipuncture (7). Using a durable fistula for an irritating intravenous agent may be preferable to squandering scarce peripheral veins.
Fistulas differ from central venous catheters in important ways. An autogenous fistula presents little infectious risk to its owner. The sterile bloodstream and the non-sterile world are not persistently connected
by a foreign body. Autogenous fistulas are quite resistant to spontaneous thrombosis. While arteriovenous grafts are less resistant, thromboses
are frequently amenable to percutaneous salvage. In contrast to a central catheter, a fistula cannot fall out of its owner. Needle sites are normally located in peripheral positions where bleeding is relatively easy to control with direct pressure. Fistula blood flow is less profuse than in the superior vena cava, and the peripheral puncture site in a fistula is of smaller diameter than the less compressible puncture site of a central catheter. The pressure inside a fistula is normally one-half of the mean arterial pressure, which is higher than the pressure inside a central vein, but substantially lower than systolic arterial pressure. Thrombocytopenia and leukopenia impact more significantly upon the risks of central venous catheters than of fistulas. With these distinctions in mind, a hemodialysis fistula emerges as a reasonable alternative to either peripheral or central venous access for chemotherapy.
Case 4 illustrates the risks of central venous catheter access in hemodialysis patients. Approximately 1 in 55 patients with central venous hemodialysis
catheters will die of infectious endocarditis (3). This patient likely had endocarditis, although transesophageal echocardiography was not performed due to esophageal irradiation. The morbidity of this infection, as well as the invasive procedures and loss of liberty required for cure, would all have been avoided if the existing fistula had been accessed for chemotherapy.
We encountered intermittent episodes of emotional resistance to fistula use among health care personnel, some of which were surprisingly intense.
This reluctance arose in part from the traditionally vociferous protection of fistulas by nephrology teams. Staff nurses emphatically trained never to
touch a fistula arm for a needlestick or a blood pressure reading were understandably concerned about using a fistula for infusion of chemotherapy.
Nephrology personnel, comfortable with fistula use and accustomed to administering multiple intravenous agents during dialyses, needed to provide
close support. Concerns were expressed about the possibility of profuse hemorrhage, skin damage due to irritants, damage to the fistula, intra-arterial administration of drugs, and potential liabilities.
Aside from one minor cutaneous ecchymosis, none of these adverse events occurred. These results cannot be generalized to all hemodialysis patients. Success may have been predicated upon all three patients having congstanding reliable fistulas. Chemotherapy access could have been far more problematic if underdeveloped or unreliable fistulas were recruited. Assessment of fistula suitability by trained renal personnel is necessary,
as is meticulous training of everyone expected to participate in use of the access site. Our findings cannot be generalized to all chemotherapeutic
agents, some of which are more potentially irritating than others.
In conclusion, we present 3 cases in which cancer chemotherapy was successfully administered via a pre-existing mature hemodialysis fistula. No infusion-related injuries occurred. No detectable decreases in solute clearance were detected, nor any damage to any of the fistulas. Catheter-related bacteremia was avoided, and venous access was not depleted.
No procedures were needed to install, replace, or remove central catheters. For selected hemodialysis patients with malignancies, the dialysis fistula is a safe alternative chemoaccess site with unique anatomic advantages over peripheral veins or central venous catheters.
REFERENCES
1. Kuter DJ. Thrombotic complications of central venous catheters in cancer patients. Oncologist 2004; 9: 207-16.
2. Naumovic RT, Jovanovic DB, Djukanovic LJ. Temporary vascular catheters for hemodialysis: a 3-year prospective study. Int J Artif Organs 2004; 27: 848-54.
3. Sandroni S, McGill R, Brouwer D. Hemodialysis catheter-associated endocarditis: clinical features, risks, and costs. Semin Dial 2003; 16: 263-5.
4. Blas A 3rd, McGill R, Sandroni S. Case 4-2002: Cancer-associated obstruction and glomerular damage. N Engl J Med 2002; 346: 1751-2.
5. Kiani A, Kohne CH, Franz T, et al. Pharmacokinetics of gemcitabine in patients with end-stage renal disease: effective clearance of its main metabolite by standard hemodialysis treatment. Cancer Chemother Pharmacol 2003; 51: 266-70.
6. Krpan D, Demarin V, Prot F, Milutinovic S, Molnar V, Milutnovic E. Measurement of blood flow through AV-fistulas by means of Doppler sonography in regularly haemodialysed patients. Int J Artif Organs 1991; 14: 78-82.
7. McGill RL, Marcus RJ, Healy DA, Brouwer DJ, Smith BC, Sandroni SE. AV fistula rates: changing the culture of vascular access. The Journal of Vascular Access 2005; 6: 13-7.(J. Harney , S. Ahmed1, K.)