Preventive Treatment Strategies Widmer MK, Malik J (eds): Patient Safety in Dialysis Access. Contrib Nephrol. Basel, Karger, 2015, vol 184, pp 51–58 DOI: 10.1159/000365822
Patient Safety in Vascular Access Patients on Hemodialysis: Contrast Agents and Renal Function Bruno Vogt Department of Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital, Bern, Switzerland
Abstract Patient safety is a major concern in medical practice. Today, the health care system is faced with a growing number of patients at increased risk with serious conditions, older patients, and multimorbidity and kidney disease. In these patients, not only the correct diagnostic but also the time to get the correct diagnosis and the strategy of treatment are of great importance. For this reason, the numbers of imaging, interventional radiological procedures and the administration of potentially nephrotoxic agents are increasing. Preventive strategies for contrast-induced side effects, especially contrast-induced renal failure, are © 2015 S. Karger AG, Basel of ‘real life’ importance.
• Always follow rule one: Does the indication for the planned examination stand up? • Always follow rule two: What is the exact question to be answered by the test? • Always follow rule three: Can the question be answered by a less invasive and/or less dangerous procedure/test? • Always follow rule one once again: Is the test indicated?
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Recommendations to Improve Patient Safety
Introduction
Radiology is an integral component in the evaluation of the kidney. For decades, the primary imaging of the urinary tract has been excretion radiography following intravenous administration of iodinated contrast media (CM). This technique is called intravenous urography or pyelography, or excretory urography. In the last 30 years, we have witnessed an extraordinary development of the renal imaging technique. Ultrasounds, with or without ultrasound CM, computed tomography (CT) with or without iodinated CM, magnetic resonance imaging (MRI), with or without gadolinium-containing CM, are used with increased frequency. The aim is to compensate for the limitations of intravenous pyelography, to limit radiation exposure, and to limit CM side effects. In the same context, a reappraisal of scintigraphic methods using radioactive tracer is observed, including positron-based techniques. And to compensate for potential side effects of CM, and to get more information from MRI, new techniques are developed. These MRI techniques are resumed in the term functional MRI, including diffusion MRI, BOLD-MRI (blood oxygen level determination MRI), or new angiography MRI methods without the use of CM. This chapter will outline the problems of CM, the iodinated for radiography and the gadolinium based for MRI, when treating patients with impaired renal function.
Contrast Media
We are in an excellent situation today that we have intravenous CM for radiography containing iodine, CM with gadolinium for MRI, and gas-containing bubbles used as CM for ultrasound examinations. This chapter will focus on iodinated and on gadolinium-containing CM, but not on the recently developed ultrasound CM. However, these new ultrasound based techniques might well replace some of the conventional techniques with CT or MRI in the future.
These contrast agents continue to have a role in many imaging techniques. A tri-iodinated benzene ring forms the chemical basis for all intravascular contrast agents for x-ray examinations. Mortality is increased in patients with acute renal failure following exposure to CM [1–3]. For this reason, strategies to reduce nephrotoxicity have been developed. The toxicity of the CM has been reduced
52
Vogt Widmer MK, Malik J (eds): Patient Safety in Dialysis Access. Contrib Nephrol. Basel, Karger, 2015, vol 184, pp 51–58 (DOI: 10.1159/000365822)
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Iodinated CM
Nephrotoxic agents 26%
Contrast agents 22%
Myeloma 13%
Pyelonephritis 8%
General factors for acute renal failure
Immunoallergic reactions 14%
Age Dehydration Vascular diseases
Cholesterol embolism 17%
by developing low- and iso-osmolar agents, and by better identification and preparation of patients with high risk for contrast-induced nephropathy (fig. 1). Despite optimal preparation in a tertiary hospital, contrast nephropathy is still a major factor for renal failure. However, one has to be aware that a clear separation between CM nephropathy and cholesterol embolism is not possible, and mixed clinical pictures can exist. This has to be clear in mind today with increasing numbers of intravascular interventions. Historically, contrast agents used to have very high osmolality. This was due to the high iodine content for increasing the contrast capacity. These agents had almost 5 times higher osmolality than normal plasma. This chemical characteristic contributes to the excellence of contrast imaging, but the high osmolality
Contrast Agents Widmer MK, Malik J (eds): Patient Safety in Dialysis Access. Contrib Nephrol. Basel, Karger, 2015, vol 184, pp 51–58 (DOI: 10.1159/000365822)
53
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Fig. 1. Acute kidney injury in noncritically ill patients admitted to a tertiary care academic center in medical and surgical services (after Meier et al. [3]).
CM Adenosin Endothelin
PGE2 PGI 2 NO
Osmotic load to distal tubule
THP viscosity
Blood viscosity Renal blood flow
Direct tubular toxicity
O2 consumption O2
Medullary hypoxia
Tubular obstruction
CM nephrotoxicity Renal failure
contributes to the toxicity. Furthermore, in the old times patients were dehydrated to get fine renal contrast images, a practice that contributed to renal failure after exposure, especially in myeloma patients: ‘Since the dehydration utilized in the preparation of patients for intravenous pyelography will tend to optimize the circumstances for precipitation of the abnormal urine proteins, it would seem reasonable to suggest that patients with myeloma should not be prepared for this examination by dehydration’ [4]. New iodinated contrast agents have been developed with the aim to give the same image quality but less toxicity. It is important to realize that the so-called low-osmolar CM do not have lower osmolality than plasma, but twice the plasma osmolality. Indeed, the term low-osmolality refers to the old CM, i.e. they are lower than the old CM that were around 1,200 mosm/l, and the low-osmolar CM are around 600 mosm/l. Isoosmolar refers to the plasma, and means that these CM are comparable to plasma osmolality, i.e. around 300 mosm/l. The high osmolality of CM explains another important feature of these agents. They are osmotic active and act similar to osmotic diuretics such as mannitol. After administration, an increased diuresis is observed. This observation supports the necessity to perform hydration of the patient not only before, but also after administration of CM to balance the CM-induced diuresis. The histological lesions in the kidney are of the same type as the lesions observed after administration of mannitol or other agents inducing osmotic diuresis.
54
Vogt Widmer MK, Malik J (eds): Patient Safety in Dialysis Access. Contrib Nephrol. Basel, Karger, 2015, vol 184, pp 51–58 (DOI: 10.1159/000365822)
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Fig. 2. Different mechanisms of renal toxicity of iodinated CM. THP = Tamm-Horsfall glycoprotein.
Medullary oxygenation decreases when iodinated CM is administrated (fig. 2). This has been shown first in animals and later in human after exposure to intravenous CM [5]. There is an important difference between rodent models and human; indeed, the human kidney is more sensitive to iodinated intravenous CM responding immediately with decreased medullary oxygenation. Strategies to minimize nephrotoxicity of CM such as the antioxidant N-acetylcysteine might have an effect through this mechanism. Interestingly, dark Swiss chocolate might increase renal medullary oxygenation in human [6]. The role in preventing CM nephropathy has not been studied. Two other factors have to be mentioned that affect renal medullary oxygen content. First with age, the renal medullary oxygenation decreases, which might increase the risk in elderly patients [7]. Second, the use of nonsteroidal anti-inflammatory drugs decreases the kidney response to hydration and might well contribute to CM-induced nephropathy by this mechanism [8].
Before administration of CM, the indication of the test should be controlled and replaced by another examination without CM if possible. If CM will be administrated in a patient with CKD or acute renal failure, lowosmolality CM should be used [9]. Correct hydration is essential. Because the CM acts as an osmotic diuretic, hydration after CM administration is as important as hydration before CM administration. For more than a decade, the classic scheme of Solomon and collaborators was highly recommended [10]. The procedure included hydration with a 0.45% NaCl i.v. solution 1 ml/kg body weight over 12 h before and 12 h after the administration of CM. The 0.45% solution has been replaced by 0.9% NaCl after the study was published, and recently bicarbonate solutions are used in a similar way [11]. This is generally accepted but the hydration might be a problem in heart failure patients. New techniques are investigated for this purpose, a promising one is the use of controlled intense hydration by a feedback loop using urinary output through the so called RenalGuard System [12]. Basically, this system matches automatically the intravenous replacement solutions to the urinary flow allowing to achieve very high urinary volumes up to 1,000 ml per hour. Today, this method is not yet entered in routine clinical practice. The role of concomitant medication is not clear due to the lack of good clinical studies [9]. It is recommended to stop nonsteroidal anti-inflammatory drugs, metformin for the risk of lactic acidosis with decreasing renal function, and diuretics. Usually, diuretics used for long-term treatment of hypertension and inhibitors of the renin-angiotensin system should not be discontinued.
Contrast Agents Widmer MK, Malik J (eds): Patient Safety in Dialysis Access. Contrib Nephrol. Basel, Karger, 2015, vol 184, pp 51–58 (DOI: 10.1159/000365822)
55
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Iodinated CM in Patients with Impaired Renal Function
80 60 >350 (n = 26)
40
250–350 (n = 32)
20 0
200 (n = 33)
100–200 (n = 30) CM dose (ml)
Patient Safety in Vascular Access Patients on Hemodialysis: Contrast Agents and Renal Function Bruno Vogt Department of Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital, Bern, Switzerland
Abstract Patient safety is a major concern in medical practice. Today, the health care system is faced with a growing number of patients at increased risk with serious conditions, older patients, and multimorbidity and kidney disease. In these patients, not only the correct diagnostic but also the time to get the correct diagnosis and the strategy of treatment are of great importance. For this reason, the numbers of imaging, interventional radiological procedures and the administration of potentially nephrotoxic agents are increasing. Preventive strategies for contrast-induced side effects, especially contrast-induced renal failure, are © 2015 S. Karger AG, Basel of ‘real life’ importance.
• Always follow rule one: Does the indication for the planned examination stand up? • Always follow rule two: What is the exact question to be answered by the test? • Always follow rule three: Can the question be answered by a less invasive and/or less dangerous procedure/test? • Always follow rule one once again: Is the test indicated?
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Recommendations to Improve Patient Safety
Introduction
Radiology is an integral component in the evaluation of the kidney. For decades, the primary imaging of the urinary tract has been excretion radiography following intravenous administration of iodinated contrast media (CM). This technique is called intravenous urography or pyelography, or excretory urography. In the last 30 years, we have witnessed an extraordinary development of the renal imaging technique. Ultrasounds, with or without ultrasound CM, computed tomography (CT) with or without iodinated CM, magnetic resonance imaging (MRI), with or without gadolinium-containing CM, are used with increased frequency. The aim is to compensate for the limitations of intravenous pyelography, to limit radiation exposure, and to limit CM side effects. In the same context, a reappraisal of scintigraphic methods using radioactive tracer is observed, including positron-based techniques. And to compensate for potential side effects of CM, and to get more information from MRI, new techniques are developed. These MRI techniques are resumed in the term functional MRI, including diffusion MRI, BOLD-MRI (blood oxygen level determination MRI), or new angiography MRI methods without the use of CM. This chapter will outline the problems of CM, the iodinated for radiography and the gadolinium based for MRI, when treating patients with impaired renal function.
Contrast Media
We are in an excellent situation today that we have intravenous CM for radiography containing iodine, CM with gadolinium for MRI, and gas-containing bubbles used as CM for ultrasound examinations. This chapter will focus on iodinated and on gadolinium-containing CM, but not on the recently developed ultrasound CM. However, these new ultrasound based techniques might well replace some of the conventional techniques with CT or MRI in the future.
These contrast agents continue to have a role in many imaging techniques. A tri-iodinated benzene ring forms the chemical basis for all intravascular contrast agents for x-ray examinations. Mortality is increased in patients with acute renal failure following exposure to CM [1–3]. For this reason, strategies to reduce nephrotoxicity have been developed. The toxicity of the CM has been reduced
52
Vogt Widmer MK, Malik J (eds): Patient Safety in Dialysis Access. Contrib Nephrol. Basel, Karger, 2015, vol 184, pp 51–58 (DOI: 10.1159/000365822)
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Iodinated CM
Nephrotoxic agents 26%
Contrast agents 22%
Myeloma 13%
Pyelonephritis 8%
General factors for acute renal failure
Immunoallergic reactions 14%
Age Dehydration Vascular diseases
Cholesterol embolism 17%
by developing low- and iso-osmolar agents, and by better identification and preparation of patients with high risk for contrast-induced nephropathy (fig. 1). Despite optimal preparation in a tertiary hospital, contrast nephropathy is still a major factor for renal failure. However, one has to be aware that a clear separation between CM nephropathy and cholesterol embolism is not possible, and mixed clinical pictures can exist. This has to be clear in mind today with increasing numbers of intravascular interventions. Historically, contrast agents used to have very high osmolality. This was due to the high iodine content for increasing the contrast capacity. These agents had almost 5 times higher osmolality than normal plasma. This chemical characteristic contributes to the excellence of contrast imaging, but the high osmolality
Contrast Agents Widmer MK, Malik J (eds): Patient Safety in Dialysis Access. Contrib Nephrol. Basel, Karger, 2015, vol 184, pp 51–58 (DOI: 10.1159/000365822)
53
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Fig. 1. Acute kidney injury in noncritically ill patients admitted to a tertiary care academic center in medical and surgical services (after Meier et al. [3]).
CM Adenosin Endothelin
PGE2 PGI 2 NO
Osmotic load to distal tubule
THP viscosity
Blood viscosity Renal blood flow
Direct tubular toxicity
O2 consumption O2
Medullary hypoxia
Tubular obstruction
CM nephrotoxicity Renal failure
contributes to the toxicity. Furthermore, in the old times patients were dehydrated to get fine renal contrast images, a practice that contributed to renal failure after exposure, especially in myeloma patients: ‘Since the dehydration utilized in the preparation of patients for intravenous pyelography will tend to optimize the circumstances for precipitation of the abnormal urine proteins, it would seem reasonable to suggest that patients with myeloma should not be prepared for this examination by dehydration’ [4]. New iodinated contrast agents have been developed with the aim to give the same image quality but less toxicity. It is important to realize that the so-called low-osmolar CM do not have lower osmolality than plasma, but twice the plasma osmolality. Indeed, the term low-osmolality refers to the old CM, i.e. they are lower than the old CM that were around 1,200 mosm/l, and the low-osmolar CM are around 600 mosm/l. Isoosmolar refers to the plasma, and means that these CM are comparable to plasma osmolality, i.e. around 300 mosm/l. The high osmolality of CM explains another important feature of these agents. They are osmotic active and act similar to osmotic diuretics such as mannitol. After administration, an increased diuresis is observed. This observation supports the necessity to perform hydration of the patient not only before, but also after administration of CM to balance the CM-induced diuresis. The histological lesions in the kidney are of the same type as the lesions observed after administration of mannitol or other agents inducing osmotic diuresis.
54
Vogt Widmer MK, Malik J (eds): Patient Safety in Dialysis Access. Contrib Nephrol. Basel, Karger, 2015, vol 184, pp 51–58 (DOI: 10.1159/000365822)
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Fig. 2. Different mechanisms of renal toxicity of iodinated CM. THP = Tamm-Horsfall glycoprotein.
Medullary oxygenation decreases when iodinated CM is administrated (fig. 2). This has been shown first in animals and later in human after exposure to intravenous CM [5]. There is an important difference between rodent models and human; indeed, the human kidney is more sensitive to iodinated intravenous CM responding immediately with decreased medullary oxygenation. Strategies to minimize nephrotoxicity of CM such as the antioxidant N-acetylcysteine might have an effect through this mechanism. Interestingly, dark Swiss chocolate might increase renal medullary oxygenation in human [6]. The role in preventing CM nephropathy has not been studied. Two other factors have to be mentioned that affect renal medullary oxygen content. First with age, the renal medullary oxygenation decreases, which might increase the risk in elderly patients [7]. Second, the use of nonsteroidal anti-inflammatory drugs decreases the kidney response to hydration and might well contribute to CM-induced nephropathy by this mechanism [8].
Before administration of CM, the indication of the test should be controlled and replaced by another examination without CM if possible. If CM will be administrated in a patient with CKD or acute renal failure, lowosmolality CM should be used [9]. Correct hydration is essential. Because the CM acts as an osmotic diuretic, hydration after CM administration is as important as hydration before CM administration. For more than a decade, the classic scheme of Solomon and collaborators was highly recommended [10]. The procedure included hydration with a 0.45% NaCl i.v. solution 1 ml/kg body weight over 12 h before and 12 h after the administration of CM. The 0.45% solution has been replaced by 0.9% NaCl after the study was published, and recently bicarbonate solutions are used in a similar way [11]. This is generally accepted but the hydration might be a problem in heart failure patients. New techniques are investigated for this purpose, a promising one is the use of controlled intense hydration by a feedback loop using urinary output through the so called RenalGuard System [12]. Basically, this system matches automatically the intravenous replacement solutions to the urinary flow allowing to achieve very high urinary volumes up to 1,000 ml per hour. Today, this method is not yet entered in routine clinical practice. The role of concomitant medication is not clear due to the lack of good clinical studies [9]. It is recommended to stop nonsteroidal anti-inflammatory drugs, metformin for the risk of lactic acidosis with decreasing renal function, and diuretics. Usually, diuretics used for long-term treatment of hypertension and inhibitors of the renin-angiotensin system should not be discontinued.
Contrast Agents Widmer MK, Malik J (eds): Patient Safety in Dialysis Access. Contrib Nephrol. Basel, Karger, 2015, vol 184, pp 51–58 (DOI: 10.1159/000365822)
55
Downloaded by: Fudan University Library 61.129.42.30 - 5/11/2015 8:50:13 PM
Iodinated CM in Patients with Impaired Renal Function
80 60 >350 (n = 26)
40
250–350 (n = 32)
20 0
200 (n = 33)
100–200 (n = 30) CM dose (ml)
