Efficacy of Argatroban in Critically Ill Patients with Heparin Resistance: A Retrospective Analysis

2015 ◽  
Vol 41 (01) ◽  
pp. 061-067 ◽  
Author(s):  
Benjamin Treichl ◽  
Mirjam Bachler ◽  
Ingo Lorenz ◽  
Barbara Friesenecker ◽  
Elgar Oswald ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Primary Objective ◽  
University Hospital ◽  
Thrombin Inhibitor ◽  
Clinical Aspects ◽  
Surgical Intensive Care ◽  
Heparin Resistance ◽  
The Mean ◽  
Prophylactic Anticoagulation

The patients who do not respond even to very high dosages of heparin are assumed to suffer from heparin resistance. The aim of this study was to investigate whether critically ill patients suffering from heparin resistance generally have low antithrombin III (AT) levels, and if the direct thrombin inhibitor argatroban in that case can be an effective option to achieve prophylactic anticoagulation. The study was conducted at the Department for General and Surgical Intensive Care Medicine at the University Hospital Innsbruck. We retrospectively included all patients between 2008 and 2012, who received argatroban because of poor response to high-dosage heparin prophylaxis. The period under observation lasted in total for 9 days, 2 days of anticoagulation with unfractionated heparin (UFH) and 7 days with argatroban. The primary objective was to investigate if after 7 (± 1) hours of switching to argatroban the activated partial thromboplastin time (aPTT) levels were in a prophylactic range of 45 to 55 seconds. Further objectives were to assess the AT level, side effects such as bleeding or thromboembolism, platelet count, correlation between organ function and argatroban dose as well as any need for allogeneic blood products. The study population, consisting of 5 women and 15 men with a mean (± standard deviation, SD) age of 54.6 ± 16.3 years, differed in many clinical aspects. A median (interquartile range) heparin dose of 1,000, 819 to 1,125 IU/h was administered for 2 days and failed in providing a prophylactic anticoagulation measured by the aPTT. The mean aPTT level with heparin treatment was 38.5 seconds (± 4.7) its change within that period was not significant. After switching to argatroban, the mean increase of the aPTT levels in all study patients amounted from 38.5 to 48.3 seconds (p < 0.001). The rise in aPTT clearly reaches sufficient prophylactic anticoagulant levels. The maintenance of prophylactic aPTT levels was achieved over the period of 1 week. There was neither a correlation found between low-AT levels and occurrence of heparin resistance, nor between the simplified acute physiology score II and the administered argatroban dose (r = −0.224, p = 0.342). The results of the present study indicate that argatroban is an effective alternative therapy, especially in critically ill patients, to achieve prophylactic anticoagulation when heparin resistance occurs.

Argatroban Dosage in Critically Ill Patients with HIT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1779-1779 ◽  
Author(s):  
Sarkis B. Baghdasarian ◽  
Inder Singh ◽  
Michael A. Militello ◽  
John R. Bartholomew ◽  
Susan M. Begelman
Keyword(s):  
Liver Disease ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Thrombin Inhibitor ◽  
Surgical Intensive Care Unit ◽  
Moderate Hepatic Impairment ◽  
Surgical Intensive Care ◽  
Hepatic Congestion ◽  
Organ System Failure ◽  
The Mean

Abstract Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy that can result in significant morbidity and mortality. Immediate discontinuation of heparin followed by the administration of a direct thrombin inhibitor (DTI) is the standard of care. There are two DTIs approved by the FDA for this indication, argatroban and lepirudin. Argatroban is metabolized in the liver by hydroxylation and aromatization and requires dosage adjustment in patients with moderate hepatic impairment defined as a Child-Pugh score >6. The normal recommended starting dose of 2 mcg/kg/min is reduced to 0.5 mcg/kg/min in these patients. Objective : Our clinical observation was that the recommended starting doses of argatroban in the ICU resulted in elevated activated partial thromboplastin time (aPTT) values that persisted for a prolonged time. This may result in a higher bleeding risk and delay life-saving invasive procedures especially in the absence of an antidote. Therefore, our objective is to show that critically ill patients without significant liver disease require a lower dosage of argatroban than recommended in the manufacturer’s prescribing information and to identify factors that may affect this recommendation. Materials and Method : Retrospective chart review of patients admitted to a medical or surgical intensive care unit (ICU), diagnosed with HIT who received argatroban for more than 24 hours. SPSS version 11.5 was used for data analysis. Results : 65 patients (37 men) were analyzed. The mean age was 65.8 years. 43% had abnormal liver function tests (LFT’s) defined as ALT>50 or bilirubin >1.5 (100% of the patients had a normal baseline INR), 24.6% had acute renal failure (ARF) and 36.9% were septic. 40% had one organ system failure (OSF), 40% had two and 20% three. The diagnosis of ARF, sepsis and the number of OSF was based on the ICU physician’s documentation and the patient’s active problem list. Excluding 3 patients with a history of liver disease (1) or acute liver decompensation (2), the mean argatroban dose for our ICU patients was 0.91 mcg/kg/min. Patients with ARF (n=16/65) required a significantly lower dose (0.65 mcg/kg/min, p=0.044), as did patients with sepsis (0.70 mcg/kg/min, p=0.03, n=24/65). Even in patients with normal LFT’s, dosage requirements were lower ranging from 1.2 mcg/kg/min with one OSF to 0.52 mcg/kg/min with three OSF (p=0.009). Discussion : Factors other than pre-existing liver disease appear to affect the dosage of argatroban in critically ill patients with HIT. Our mean dose to achieve a therapeutic aPTT was 0.91 mcg/kg/min with even lower doses in patients with ARF, sepsis or more than one OSF. This may be explained by the influence of ARF, sepsis, or OSF on argatroban metabolism by the liver that is not necessarily reflected in ALT, bilirubin, or even INR measurements. This metabolic effect may be due to passive hepatic congestion, accumulation of certain metabolites or interaction with the multiple medications used in these patients. Consideration should be given to initiate argatroban at a lower dosage in the critically ill patient.

scholarly journals A Prospective Pilot Trial to Assess the Efficacy of Argatroban (Argatra®) in Critically Ill Patients with Heparin Resistance †

2020 ◽  
Vol 9 (4) ◽  
pp. 963 ◽  
Author(s):  
Mirjam Bachler ◽  
Tobias Hell ◽  
Johannes Bösch ◽  
Benedikt Treml ◽  
Bettina Schenk ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Treatment Success ◽  
Pilot Trial ◽  
Treatment Phase ◽  
Thromboembolic Complications ◽  
Treatment Groups ◽  
Heparin Resistance ◽  
Significant Difference ◽  
Prophylactic Anticoagulation

The current study aims to evaluate whether prophylactic anticoagulation using argatroban or an increased dose of unfractionated heparin (UFH) is effective in achieving the targeted activated partial thromboplastin time (aPTT) of more than 45 s in critically ill heparin-resistant (HR) patients. Patients were randomized either to continue receiving an increased dose of UFH, or to be treated with argatroban. The endpoints were defined as achieving an aPTT target of more than 45 s at 7 h and 24 h. This clinical trial was registered on clinicaltrials.gov (NCT01734252) and on EudraCT (2012-000487-23). A total of 42 patients, 20 patients in the heparin and 22 in the argatroban group, were included. Of the patients with continued heparin treatment 55% achieved the target aPTT at 7 h, while only 40% of this group maintained the target aPTT after 24 h. Of the argatroban group 59% reached the target aPTT at 7 h, while at 24 h 86% of these patients maintained the targeted aPTT. Treatment success at 7 h did not differ between the groups (p = 0.1000), whereas at 24 h argatroban showed significantly greater efficacy (p = 0.0021) than did heparin. Argatroban also worked better in maintaining adequate anticoagulation in the further course of the study. There was no significant difference in the occurrence of bleeding or thromboembolic complications between the treatment groups. In the case of heparin-resistant critically ill patients, argatroban showed greater efficacy than did an increased dose of heparin in achieving adequate anticoagulation at 24 h and in maintaining the targeted aPTT goal throughout the treatment phase.

scholarly journals Measurement of the nociceptive flexion reflex threshold in critically ill patients – a randomized observational pilot study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Benedikt Schick ◽  
Benjamin Mayer ◽  
Steffen Walter ◽  
Sascha Gruss ◽  
Ronald Stitz ◽  
...  
Keyword(s):  
Pilot Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
University Hospital ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Mechanically Ventilated ◽  
Flexion Reflex ◽  
Nociceptive Flexion Reflex ◽  
Reflex Threshold

Abstract Background Pain detection and treatment is a major challenge in the care of critically ill patients, rendered more complex by the need to take into consideration the risk of insufficient or excessive analgesia. The nociceptive flexion reflex threshold (NFRT) has become the established basis for measuring the level of analgesia in the perioperative context. However, it remains unclear whether NFRT measurement can be usefully applied to mechanically ventilated, analgosedated critically ill patients who are unable to communicate. Therefore, the aim of the present study was to investigate whether there is an association between the NFRT measurement and the Behavioral Pain Scale (BPS) in critically ill, analgosedated, and mechanically ventilated patients and whether the NFRT measurement can also detect potential excessive analgesia. Methods This prospective, observational, randomized single-center pilot study included patients admitted to the surgical Intensive Care Unit of University Hospital Ulm, Germany, all of whom were analgosedated and intubated. Major exclusion criteria were defined as the need for the administration of neuromuscular blocking agents or neurological diseases associated with peripheral nerve conduction restriction. Initial NFRT and BPS measurements were conducted within 12 h after admission. A structured pain assessment was performed at least twice daily until extubation throughout the observation period thereafter (Group A: BPS + NFRT, Group B: BPS). Results 114 patients were included in the study. NFRT is associated negatively with BPS. NFRT was almost twice as high in patients with a Richmond Agitation Sedation Scale (RASS) score of -5 than in patients with a RASS score ≥ -4 (RASS -5 – NFRT: 59.40 vs. RASS -4 – NFRT: 29.00, p < 0.001). Conclusions NFRT measurement is associated negatively with the BPS in critically ill patients. NFRT measurement provides guidance for the evaluation of nociceptive processes in patients with RASS scores ≤ −4, in whom analgesia level is often difficult to assess. However, in order to identify excessive analgesia and derive therapeutic consequences, it is necessary to gradually decrease analgesics and sedatives until a stimulus threshold is reached at which the patient does not feel pain. Trial Registration Retrospectively registered in the German Clinical Trials Register, registration number DRKS00021149, date of registration: March 26, 2020. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021149.

scholarly journals Predictors of QT Interval Prolongation in Critically-ill Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine

2020 ◽  
Author(s):  
Frederico Scuotto ◽  
Rogério Marra ◽  
Lilian Leite de Almeida ◽  
Mariana Santa Rita Soares ◽  
Gabriela Kurita Silva ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Qt Interval ◽  
Clinical Aspects ◽  
Multivariable Logistic Regression Analysis ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Qt Interval Prolongation ◽  
The Mean ◽  
Interval Enlargement

AbstractBackgroundHydroxychloroquine (HCQ) has been described as a potential treatment for SARS-CoV-2 infection. However, there are safety concerns regarding its QT interval and pro-arrhythmic effects.ObjectiveThis trial aimed to determine the predictors of QT interval prolongation and pro-arrhythmic effects in patients hospitalized for SARS-CoV-2 infection and receiving HCQ.MethodsWe performed a retrospective observational study of 45 critically-ill patients hospitalized because of SARS-CoV-2 infection and treated with 800 mg of HCQ at day 1 and 400 mg on days 2–5. Clinical aspects and outcomes, basal and final corrected QT (QTc) interval, and the incidence of arrhythmias and arrhythmogenic death were observed. Independent predictors of QTc prolongation were identified using multivariable logistic regression analysis. QT interval prolongation was considered substantial at final QTc ≥ 480 ms.ResultsThe mean age was 60.9 ± 16.67 years and 28 (62.2%) patients were men. Basal QTc was 442 ± 28 ms, and the final QTc interval was 458 ± 34 ms, for a mean QTc interval variation of 15 ± 11 ms. There was no arrhythmogenic death. The need for hemodialysis remained a statistically significant predictor of QT interval enlargement (odds ratio, 10.34; 95% confidence interval, 1.04 – 102.18; p = 0.045).ConclusionsHCQ promotes mild to moderate QT interval prolongation. The risk of QT interval prolongation is higher among patients with acute renal failure requiring hemodialysis.

scholarly journals AChE-activity in critically ill patients with suspected septic encephalopathy: a prospective, single-centre study

2020 ◽  
Author(s):  
Benedikt Zujalovic ◽  
Benjamin Mayer ◽  
Sebastian Hafner ◽  
Florian Balling ◽  
Eberhard Barth
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Repeated Measures ◽  
Acetylcholinesterase Activity ◽  
University Hospital ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Baseline Values

Abstract Background In consequence of systemic inflammation, up to 70% of septic patients develop a diffuse brain dysfunction, accompanying with an increase in mortality, which is referred to as “septic associated encephalopathy”. Subsuming septic associated encephalopathy as a category of delirium, there is a common pathophysiology (neuro-inflammation and cholinergic transmitter imbalance). This can be approximated by measuring the acetylcholinesterase activity as a surrogate parameter of cholinergic activity. However, conflicting results for acetylcholinesterase activity exists, if single-point measurements have been done. Therefore, we wanted to test the hypothesis, whether longitudinal analysis of acetylcholinesterase activity in Intensive Care Unit patients displays septic associated encephalopathy/delirium in septic patients and reveals significant differences in comparison with non-septic, critically ill patients.Methods In this prospective, observational, single-center study, 175 patients, admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany, were included. Patients were divided into septic (n = 45) and non-septic (n = 130) patients and were screened for delirium/cognitive dysfunction. Subgroups for patients with delirium and altered acetylcholinesterase activity were built, dependent if an increase/decrease of the acetylcholinesterase activity was observed. Acetylcholinesterase activity was analysed over the course of time by using a linear regression model accounting for repeated measures. By using a time adjusted model, the effect of further possible predictors of acetylcholinesterase activity was analyzed. For nonparametric distributions, quantitative data were compared using Wilcoxon matched-pairs test. For the analysis of the independent samples, we used the Mann-Whitney test. Results There was a statistically significant, time-dependent change in acetylcholinesterase activity (decrease/increase) over a period of at least 5 days in septic patients which revealed septic associated encephalopathy/delirium in about 90%.Conclusion The longitudinal measurement of acetylcholinesterase activity over several consecutive days revealed a shift compared to baseline values exclusively in septic patients with septic associated encephalopathy/delirium. Acetylcholinesterase activity alteration compared to baseline values at the onset of sepsis may help to detect and differentiate septic associated encephalopathy from other delirium entities.Trial registration Retrospectively registered at German Clincial Trials Register, registration number DRKS 00020542, date of registration: January 27, 2020

scholarly journals AChE-activity in critically ill patients with suspected septic encephalopathy: a prospective, single-centre study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Benedikt Zujalovic ◽  
Benjamin Mayer ◽  
Sebastian Hafner ◽  
Florian Balling ◽  
Eberhard Barth
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Ache Activity ◽  
Acetylcholinesterase Activity ◽  
Repeated Measurements ◽  
Time Dependent ◽  
University Hospital ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Longitudinal Measurement

Abstract Background Up to 70% of septic patients develop a diffuse brain dysfunction named “septic associated encephalopathy” which is often solely based on clinical impressions. However, the diagnosis of septic associated encephalopathy is outcome-relevant due to an increase in mortality in these patients. Neuroinflammation as well as a disturbance of cholinergic transmission are assumed to be the causes of both delirium and septic associated encephalopathy. An alteration in cholinergic activity can be objectified by measuring the erythrocytic acetylcholinesterase-activity. Single-point measurements of acetylcholinesterase-activity are of limited value because individual and dynamic changes over time have to be anticipated. Therefore, the hypothesis should be tested whether a longitudinal analysis of acetylcholinesterase-activity in critically ill patients can help to diagnose a suspected septic-associated encephalopathy and whether acetylcholinesterase-activity differs in comparison to non-septic patients. Methods In this prospective, observational, single-center study, 175 patients (45 with sepsis, 130 without sepsis) were included. All patients were admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany. Patients were examined daily for the presence of delirium using the CAM-ICU. Daily measurement of the acetylcholinesterase-activity was performed in all patients. The possible time-dependent change in acetylcholinesterase-activity was analyzed with a linear regression model considering repeated measurements. Using a time-adjusted model further factors able to affect AChE-activity were investigated. For nonparametric distributions quantitative data were compared using Wilcoxon matched-pairs test. For analysis of independent samples the Mann-Whitney test was performed. Results About 90% of septic patients with suspected septic associated encephalopathy exhibited a statistically significant time-dependent in- or decrease in acetylcholinesterase-activity over a period of at least 5 consecutive days. Conclusion Longitudinal measurement of acetylcholinesterase-activity over several consecutive days revealed a change from baseline only in septic patients with suspected septic-associated encephalopathy. Therefore, longitudinal measurement of acetylcholinesterase-activity is able to diagnose septic associated encephalopathy in septic patients with delirious symptoms. Trial registration Retrospectively registered at German Clinical Trials Register, registration number DRKS00020542, date of registration: January 27, 2020.

scholarly journals AChE-activity in critically ill patients with suspected septic encephalopathy: a prospective, single-centre study

2020 ◽  
Author(s):  
Benedikt Zujalovic ◽  
Benjamin Mayer ◽  
Sebastian Hafner ◽  
Florian Balling ◽  
Eberhard Barth
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Acetylcholinesterase Activity ◽  
Brain Dysfunction ◽  
Repeated Measurements ◽  
University Hospital ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Longitudinal Measurement ◽  
Single Centre Study

Abstract Background Up to 70% of septic patients develop a diffuse brain dysfunction accompanying with an increase in mortality, which is referred to as “septic associated encephalopathy”. Neuroinflammation as well as a disturbance of cholinergic transmission are assumed to be the causes of both delirium and septic associated encephalopathy. A possible change in cholinergic activity can be objectified by measuring the erythrocytic acetylcholinesterase activity. It has been shown, however, that the acetylcholinesterase activity, if only single measurements are carried out, is controversial in its significance. Therefore, we wanted to test the hypothesis whether a longitudinal analysis of acetylcholinesterase activity in critically ill patients can help to diagnose a suspected septic-associated encephalopathy and whether acetylcholinesterase activity differs in comparison to non-septic patients.Methods In this prospective, observational, single-center study, 175 patients, admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany, were included. 45 patients were septic, 130 patients were non septic. All patients were examined daily for the presence of delirium using the CAM-ICU. Daily measurement of the acetylcholinesterase activity was performed in all patients. The acetylcholinesterase activity was analyzed over time using a linear regression model taking into account repeated measurements. By using a time adjusted model, the effect of further possible predictors of acetylcholinesterase activity was analyzed too. For nonparametric distributions quantitative data were compared using Wilcoxon matched-pairs test. For the analysis of the independent samples the Mann-Whitney test was performed. Results In approximately 90% of the septic patients with suspected septic associated encephalopathy a statistically significant, time-dependent in- or decrease in acetylcholinesterase activity could be demonstrated over a period of at least 5 consecutive days.Conclusion The longitudinal measurement of acetylcholinesterase activity over several consecutive days revealed a shift compared to baseline values exclusively in septic patients with supposed septic associated encephalopathy. Therefore, longitudinal measurement of acetylcholinesterase activity may help to diagnose septic associated encephalopathy in patients with sepsis and accompanying delirium symptoms.Trial registration Retrospectively registered at German Clincial Trials Register, registration number DRKS 00020542, date of registration: January 27, 2020

scholarly journals Heparin Resistance in ECMO and the Role of Direct Thrombin Inhibitors: A Case Report

2021 ◽  
Author(s):  
Mohsyn Imran Malik ◽  
Dr. Roman Nepomuceno ◽  
Dr. Dave Nagpal
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Therapeutic Potential ◽  
Standard Procedure ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Bleeding Events ◽  
Heparin Resistance

Extracorporeal membrane oxygenation (ECMO) is a potentially life-saving technology that can provide timely support to those failing to oxygenate their blood, either due to cardiac or respiratory related illnesses. However, ECMO also requires a careful hemostatic balance due to the thrombotic nature of the external circuit and the potential for bleeding events while anticoagulated. Current standard procedure for anticoagulating patients on ECMO is the use of unfractionated heparin. Despite its widespread use, many patients still face bleeding and/or clotting complications during their admission, some resulting in disastrous consequences. One possible etiology for this ineffectiveness is due to the mechanism by which heparin works via antithrombin (AT) and the AT deficiency of a critically ill patients. In this case study, we discuss the use of an alternative anticoagulant, a direct-thrombin inhibitor (DTI) in a patient cannulated to ECMO, which is independent of AT. The case study follows their course while on ECMO, focusing on relevant hemostatic measures. We further demonstrate the therapeutic potential for DTIs in place of UFH in ECMO patients, and the need for further research into anticoagulation strategies in critically ill patients.

scholarly journals AChE-activity in critically ill patients with suspected septic encephalopathy: a prospective, single-centre study

2020 ◽  
Author(s):  
Benedikt Zujalovic ◽  
Benjamin Mayer ◽  
Sebastian Hafner ◽  
Florian Balling ◽  
Eberhard Barth
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Ache Activity ◽  
Acetylcholinesterase Activity ◽  
Repeated Measurements ◽  
Time Dependent ◽  
University Hospital ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Longitudinal Measurement

Abstract Background Up to 70% of septic patients develop a diffuse brain dysfunction named “septic associated encephalopathy” which is often solely based on clinical impressions. However, the diagnosis of septic associated encephalopathy is outcome-relevant due to an increase in mortality in these patients. Neuroinflammation as well as a disturbance of cholinergic transmission are assumed to be the causes of both delirium and septic associated encephalopathy. An alteration in cholinergic activity can be objectified by measuring the erythrocytic acetylcholinesterase-activity. Single-point measurements of acetylcholinesterase-activity are of limited value because individual and dynamic changes over time have to be anticipated. Therefore, the hypothesis should be tested whether a longitudinal analysis of acetylcholinesterase-activity in critically ill patients can help to diagnose a suspected septic-associated encephalopathy and whether acetylcholinesterase-activity differs in comparison to non-septic patients.Methods In this prospective, observational, single-center study, 175 patients (45 with sepsis, 130 without sepsis) were included. All patients were admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany. Patients were examined daily for the presence of delirium using the CAM-ICU. Daily measurement of the acetylcholinesterase-activity was performed in all patients. The possible time-dependent change in acetylcholinesterase-activity was analyzed with a linear regression model considering repeated measurements. Using a time-adjusted model further factors able to affect AChE-activity were investigated. For nonparametric distributions quantitative data were compared using Wilcoxon matched-pairs test. For analysis of independent samples the Mann-Whitney test was performed.Results About 90% of septic patients with suspected septic associated encephalopathy exhibited a statistically significant time-dependent in- or decrease in acetylcholinesterase-activity over a period of at least 5 consecutive days.Conclusion Longitudinal measurement of acetylcholinesterase-activity over several consecutive days revealed a change from baseline only in septic patients with suspected septic-associated encephalopathy. Therefore, longitudinal measurement of acetylcholinesterase-activity is able to diagnose septic associated encephalopathy in septic patients with delirious symptoms.Trial registration Retrospectively registered at German Clinical Trials Register, registration number DRKS 00020542, date of registration: January 27, 2020

scholarly journals AChE-activity in critically ill patients with suspected septic encephalopathy: a prospective, single-centre study

2020 ◽  
Author(s):  
Benedikt Zujalovic ◽  
Benjamin Mayer ◽  
Sebastian Hafner ◽  
Florian Balling ◽  
Eberhard Barth
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Ache Activity ◽  
Acetylcholinesterase Activity ◽  
Repeated Measurements ◽  
Time Dependent ◽  
University Hospital ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Longitudinal Measurement

Abstract Background: Up to 70% of septic patients develop a diffuse brain dysfunction named “septic associated encephalopathy” (SAE) which is often solely based on clinical impressions. However, the diagnosis of SAE is outcome-relevant due to an increase in mortality in these patients. Neuroinflammation as well as a disturbance of cholinergic transmission are assumed to be the causes of both delirium and septic associated encephalopathy. An alteration in cholinergic activity can be objectified by measuring the erythrocytic acetylcholinesterase-activity (AChE-activity). Single-point measurements of acetylcholinesterase-activity are of limited value because individual and dynamic changes over time have to be anticipated. Therefore, the hypothesis should be tested whether a longitudinal analysis of acetylcholinesterase-activity in critically ill patients can help to diagnose a suspected septic-associated encephalopathy and whether acetylcholinesterase-activity differs in comparison to non-septic patients.Methods: In this prospective, observational, single-center study, 175 patients (45 with sepsis, 130 without sepsis) were included. All patients were admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany. Patients were examined daily for the presence of delirium using the CAM-ICU. Daily measurement of the acetylcholinesterase-activity was performed in all patients. The possible time-dependent change in acetylcholinesterase-activity was analyzed with a linear regression model considering repeated measurements. Using a time-adjusted model, further factors able to affect AChE-activity were investigated. For nonparametric distributions quantitative data were compared using Wilcoxon matched-pairs test. For analysis of independent samples the Mann-Whitney test was performed.Results: About 90% of septic patients with suspected septic associated encephalopathy exhibited a statistically significant time-dependent in- or decrease in acetylcholinesterase-activity over a period of at least 5 consecutive days.Conclusion: Longitudinal measurement of acetylcholinesterase-activity over several consecutive days revealed a change from baseline only in septic patients with suspected septic-associated encephalopathy. Therefore, longitudinal measurement of acetylcholinesterase-activity is able to diagnose septic associated encephalopathy in septic patients with delirious symptoms.Trial registration: Retrospectively registered at German Clinical Trials Register, registration number DRKS 00020542, date of registration: January 27, 2020

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