J.T. Kielstein

Medikamentendosierung unter extrakorporaler Therapie

BACKGROUND The dosing of drugs in critically ill patients remains challenging. While increased volume of distribution after fluid resuscitation and increased cardiac output can increase clearance of antibiotics, liver failure and renal failure can decrease the clearance of drugs. If an extracorporeal device is used, the dosing of drugs becomes even more difficult. Even in intensive care patients with intact renal function, pharmacokinetics and pharmacodynamics are significantly altered. CURRENT SITUATION While there are direct readouts such as the mean arterial pressure for catecholamine therapy and measurement of serum glucose to guide insulin dosing, we lack such prompt readouts for dosing of antibiotics. In this manuscript, the principles and basic knowledge needed to improve dosing of anti-infective agents in critically ill patients undergoing extracorporeal treatment are described. Examples are the rapid utility assessment drug dosing reference books and online resources including the vancomycin test. Potential problems of extracorporeal membrane oxygenation and adsober therapy associated with renal replacement therapy are also addressed. CONCLUSION The importance of therapeutic drug monitoring is discussed. Global initiatives to increase quantity and quality of pharmacokinetic studies in this patient population through incentives and guidance of the regulatory agencies, as well as the major unmet educational need to integrate basic knowledge in this field into residency and fellowship programs as well as CME are briefly mentioned.ZusammenfassungHintergrundDie Dosierung von Medikamenten bei Intensivpatienten bleibt eine Herausforderung. Während die Dosis von Katecholaminen oder Insulin nach dem biologischen Effekt, also dem mittleren arteriellen Blutdruck oder dem Blutzucker gesteuert werden kann, ist die Anpassung der Dosis von Antibiotika an die Intensität der Nierenersatztherapie deutlich schwieriger. Selbst bei Intensivpatienten mit intakter Nierenfunktion ist die Pharmakokinetik und Pharmakodynamik deutlich verändert.ProblemstellungAufgrund eines höheren Verteilungsvolumens („fluid rescucitation“, „capillary leak“) oder einer Hypalbuminämie kann die wirksame Konzentration eines Antibiotikums deutlich vermindert sein. Kommt ein Nierenfunktionsverlust hinzu, wird das Problem noch komplexer und die Dosierung der Antibiotika noch schwieriger, da nur bei wenigen Antibiotika die Möglichkeit des Drug Monitorings besteht. Dosierungsempfehlungen beruhen häufig, auch in der aktuellen Version, auf Verfahren mit heute nicht mehr eingesetzten Filtern und Intensitäten und sind somit häufig nicht mehr zutreffend. Dies ist durch den sog. Vancomycin-Test einfach festzustellen.AusblickLangfristig wird eine Ausweitung des therapeutischen Drug Monitorings in dieser Patientenpopulation notwendig werden. Dies allein reicht aber sicher nicht aus, um patientennahe relevante Endpunkte, wie Beatmungszeit oder Tod, zu beeinflussen, sondern kann nur Ausgangspunkt für eine Qualitätsverbesserung im Bereich Infektiologie/Mikrobiologie/Pharmakotherapie sein. Um das notwendige Wissensfundament hierfür zu legen, sollte diese Problematik auch vermehrt Eingang in die Fort- und Weiterbildungspläne der entsprechenden Facharztdisziplinen aber auch in die CME Programme finden.AbstractBackgroundThe dosing of drugs in critically ill patients remains challenging. While increased volume of distribution after fluid resuscitation and increased cardiac output can increase clearance of antibiotics, liver failure and renal failure can decrease the clearance of drugs. If an extracorporeal device is used, the dosing of drugs becomes even more difficult. Even in intensive care patients with intact renal function, pharmacokinetics and pharmacodynamics are significantly altered.Current situationWhile there are direct readouts such as the mean arterial pressure for catecholamine therapy and measurement of serum glucose to guide insulin dosing, we lack such prompt readouts for dosing of antibiotics. In this manuscript, the principles and basic knowledge needed to improve dosing of anti-infective agents in critically ill patients undergoing extracorporeal treatment are described. Examples are the rapid utility assessment drug dosing reference books and online resources including the vancomycin test. Potential problems of extracorporeal membrane oxygenation and adsober therapy associated with renal replacement therapy are also addressed.ConclusionThe importance of therapeutic drug monitoring is discussed. Global initiatives to increase quantity and quality of pharmacokinetic studies in this patient population through incentives and guidance of the regulatory agencies, as well as the major unmet educational need to integrate basic knowledge in this field into residency and fellowship programs as well as CME are briefly mentioned.

[Allopurinol-induced hypersensitivity syndrome resulting in death].

The present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome (AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.ZusammenfassungDie vorliegende Kasuistik schildert den Fall eines 67-jährigen Patienten, der ein allopurinolinduziertes Hypersensitivitätssyndrom (AHS) mit toxisch- epidermaler Nekrolyse entwickelte und in der Folge an einem septischen Multiorganversagen verstarb. Mit dieser Falldarstellung soll in Anbetracht der zunehmenden Verschreibungshäufigkeit von Allopurinol die unterschätzte Gefahr eines AHS demonstriert werden.AbstractThe present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome (AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.

Plasmaaustausch im therapierefraktären septischen Schock@@@Plasma exchange in treatment refractory septic shock: Vorstellung einer Add-on-Therapiestrategie@@@Presentation of a therapeutic add-on strategy

ZusammenfassungSepsis ist eine systemische Inflammationsreaktion des Organismus auf eine – häufig lokale – Infektion, für die es gegenwärtig keine zugelassene spezifische pharmakologische Therapie gibt. Daher wird neben der Sanierung des Infektfokus und der antiinfektiven Therapie mit verschiedenen extrakorporalen Verfahren versucht, die erhöhten zirkulierenden Spiegel schädigender Mediatoren zu reduzieren. Hierfür werden zunehmend Adsorber eingesetzt, die aber nicht den gleichzeitigen Ersatz verbrauchter protektiver Faktoren ermöglichen. Der Plasmaaustausch stellt hingegen ein Verfahren dar, das sowohl die Entfernung von proinflammatorischen Mediatoren als auch die Substitution protektiver Faktoren erlaubt. Nachfolgend wird der Fall eines septischen Schocks geschildert, bei der die Plasmapherese zu einer prompten klinischen Besserung führte. Ferner wird die gegenwärtige Studienlage hierzu zusammengefasst.AbstractSepsis is defined as a systemic inflammatory response of the body to an infection. Besides anti-infective drugs and removal of the site of infection, no specific therapeutics that target the overwhelming host response are available. Clinical researchers are currently evaluating the extracorporeal elimination of circulating cytokines. Modern adsorbing techniques have increasingly been used for this purpose allowing an unselective but highly effective removal of the vast majority of circulating cytokines but also fail to replace used protective factors in patients’ plasma. Therapeutic plasma exchange (TPE) however might represent a novel method to remove pathologically elevated cytokines and simultaneously to replace protective plasmatic factors. Here we report the case of a septic shock patient treated with TPE and review the available literature with respect to TPE as an adjunctive therapy in sepsis.

Plasmaaustausch im therapierefraktären septischen Schock

ZusammenfassungSepsis ist eine systemische Inflammationsreaktion des Organismus auf eine – häufig lokale – Infektion, für die es gegenwärtig keine zugelassene spezifische pharmakologische Therapie gibt. Daher wird neben der Sanierung des Infektfokus und der antiinfektiven Therapie mit verschiedenen extrakorporalen Verfahren versucht, die erhöhten zirkulierenden Spiegel schädigender Mediatoren zu reduzieren. Hierfür werden zunehmend Adsorber eingesetzt, die aber nicht den gleichzeitigen Ersatz verbrauchter protektiver Faktoren ermöglichen. Der Plasmaaustausch stellt hingegen ein Verfahren dar, das sowohl die Entfernung von proinflammatorischen Mediatoren als auch die Substitution protektiver Faktoren erlaubt. Nachfolgend wird der Fall eines septischen Schocks geschildert, bei der die Plasmapherese zu einer prompten klinischen Besserung führte. Ferner wird die gegenwärtige Studienlage hierzu zusammengefasst.AbstractSepsis is defined as a systemic inflammatory response of the body to an infection. Besides anti-infective drugs and removal of the site of infection, no specific therapeutics that target the overwhelming host response are available. Clinical researchers are currently evaluating the extracorporeal elimination of circulating cytokines. Modern adsorbing techniques have increasingly been used for this purpose allowing an unselective but highly effective removal of the vast majority of circulating cytokines but also fail to replace used protective factors in patients’ plasma. Therapeutic plasma exchange (TPE) however might represent a novel method to remove pathologically elevated cytokines and simultaneously to replace protective plasmatic factors. Here we report the case of a septic shock patient treated with TPE and review the available literature with respect to TPE as an adjunctive therapy in sepsis.

[Plasma exchange in treatment refractory septic shock : Presentation of a therapeutic add-on strategy].

ZusammenfassungSepsis ist eine systemische Inflammationsreaktion des Organismus auf eine – häufig lokale – Infektion, für die es gegenwärtig keine zugelassene spezifische pharmakologische Therapie gibt. Daher wird neben der Sanierung des Infektfokus und der antiinfektiven Therapie mit verschiedenen extrakorporalen Verfahren versucht, die erhöhten zirkulierenden Spiegel schädigender Mediatoren zu reduzieren. Hierfür werden zunehmend Adsorber eingesetzt, die aber nicht den gleichzeitigen Ersatz verbrauchter protektiver Faktoren ermöglichen. Der Plasmaaustausch stellt hingegen ein Verfahren dar, das sowohl die Entfernung von proinflammatorischen Mediatoren als auch die Substitution protektiver Faktoren erlaubt. Nachfolgend wird der Fall eines septischen Schocks geschildert, bei der die Plasmapherese zu einer prompten klinischen Besserung führte. Ferner wird die gegenwärtige Studienlage hierzu zusammengefasst.AbstractSepsis is defined as a systemic inflammatory response of the body to an infection. Besides anti-infective drugs and removal of the site of infection, no specific therapeutics that target the overwhelming host response are available. Clinical researchers are currently evaluating the extracorporeal elimination of circulating cytokines. Modern adsorbing techniques have increasingly been used for this purpose allowing an unselective but highly effective removal of the vast majority of circulating cytokines but also fail to replace used protective factors in patients’ plasma. Therapeutic plasma exchange (TPE) however might represent a novel method to remove pathologically elevated cytokines and simultaneously to replace protective plasmatic factors. Here we report the case of a septic shock patient treated with TPE and review the available literature with respect to TPE as an adjunctive therapy in sepsis.

Erfolgreiche Hämodialyse bei lebensbedrohlicher CarbamazepinintoxikationSuccessful hemodialysis for life-threatening carbamazepine drug overdose

BACKGROUND Over the last decade, there has been a paradigm shift in the extracorporeal treatment of intoxications. The availability of new treatment options, especially new membranes has led to a decrease in the use of techniques like charcoal hemoperfusion, once considered the gold standard to eliminate highly protein bound substances. EXTRIP GUIDELINES The EXtracorporeal Treatments In Poisoning (EXTRIP) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians, and nephrologists that is reviewing all available evidence in extracorporeal procedures for the treatment of poisonings in a standardized way to distill treatment recommendations for the physician at the bedside. One of the first available EXTRIP guidelines summarizes treatment recommendations for severe carbamazepine intoxications. CASE REPORT We report the case of a 43-year-old Caucasian woman with who ingested about 21 g carbamazepine in a suicidal attempt together with alcohol. Combining gastroscopic removal of carbamazepine and multiple dose activated charcoal with intermittent high-flux hemodialysis lowered the initial carbamazepine level of 56.5 mg/l (47 mg/l before dialysis) to 25 mg/l. The patient, who initially required mechanical ventilation could be transferred to the psychiatric ward 24 h after ICU admission.

Erfolgreiche Hämodialyse bei lebensbedrohlicher Carbamazepinintoxikation@@@Successful hemodialysis for life-threatening carbamazepine drug overdose: Vorstellung neuer Leitlinien anhand eines Fallberichts@@@Case-based introduction of new guidelines

BACKGROUND Over the last decade, there has been a paradigm shift in the extracorporeal treatment of intoxications. The availability of new treatment options, especially new membranes has led to a decrease in the use of techniques like charcoal hemoperfusion, once considered the gold standard to eliminate highly protein bound substances. EXTRIP GUIDELINES The EXtracorporeal Treatments In Poisoning (EXTRIP) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians, and nephrologists that is reviewing all available evidence in extracorporeal procedures for the treatment of poisonings in a standardized way to distill treatment recommendations for the physician at the bedside. One of the first available EXTRIP guidelines summarizes treatment recommendations for severe carbamazepine intoxications. CASE REPORT We report the case of a 43-year-old Caucasian woman with who ingested about 21 g carbamazepine in a suicidal attempt together with alcohol. Combining gastroscopic removal of carbamazepine and multiple dose activated charcoal with intermittent high-flux hemodialysis lowered the initial carbamazepine level of 56.5 mg/l (47 mg/l before dialysis) to 25 mg/l. The patient, who initially required mechanical ventilation could be transferred to the psychiatric ward 24 h after ICU admission.

Erfolgreiche Hämodialyse bei lebensbedrohlicher Carbamazepinintoxikation

BACKGROUND Over the last decade, there has been a paradigm shift in the extracorporeal treatment of intoxications. The availability of new treatment options, especially new membranes has led to a decrease in the use of techniques like charcoal hemoperfusion, once considered the gold standard to eliminate highly protein bound substances. EXTRIP GUIDELINES The EXtracorporeal Treatments In Poisoning (EXTRIP) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians, and nephrologists that is reviewing all available evidence in extracorporeal procedures for the treatment of poisonings in a standardized way to distill treatment recommendations for the physician at the bedside. One of the first available EXTRIP guidelines summarizes treatment recommendations for severe carbamazepine intoxications. CASE REPORT We report the case of a 43-year-old Caucasian woman with who ingested about 21 g carbamazepine in a suicidal attempt together with alcohol. Combining gastroscopic removal of carbamazepine and multiple dose activated charcoal with intermittent high-flux hemodialysis lowered the initial carbamazepine level of 56.5 mg/l (47 mg/l before dialysis) to 25 mg/l. The patient, who initially required mechanical ventilation could be transferred to the psychiatric ward 24 h after ICU admission.

[Successful hemodialysis for life-threatening carbamazepine drug overdose: Case-based introduction of new guidelines].

BACKGROUND Over the last decade, there has been a paradigm shift in the extracorporeal treatment of intoxications. The availability of new treatment options, especially new membranes has led to a decrease in the use of techniques like charcoal hemoperfusion, once considered the gold standard to eliminate highly protein bound substances. EXTRIP GUIDELINES The EXtracorporeal Treatments In Poisoning (EXTRIP) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians, and nephrologists that is reviewing all available evidence in extracorporeal procedures for the treatment of poisonings in a standardized way to distill treatment recommendations for the physician at the bedside. One of the first available EXTRIP guidelines summarizes treatment recommendations for severe carbamazepine intoxications. CASE REPORT We report the case of a 43-year-old Caucasian woman with who ingested about 21 g carbamazepine in a suicidal attempt together with alcohol. Combining gastroscopic removal of carbamazepine and multiple dose activated charcoal with intermittent high-flux hemodialysis lowered the initial carbamazepine level of 56.5 mg/l (47 mg/l before dialysis) to 25 mg/l. The patient, who initially required mechanical ventilation could be transferred to the psychiatric ward 24 h after ICU admission.

Kennen Sie die sieben Todsünden

Es bleibt wohl einem Protestanten vorbehalten, die Todsünde (peccatum mortiferum) in den Bereich der Medizin zu übertragen. Unverzeihliche Fehler bei der Auswahl und/oder Dosierung von Medikamenten können aber bei Patienten mit chronischer Nierenkrankheit dramatische Folgen haben, die bis zum Tode führen.