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

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.

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Measurement of the nociceptive flexion reflex threshold in critically ill patients - a monocentric prospective observational study

10.21203/rs.3.rs-199232/v1 ◽

2021 ◽

Author(s):

Benedikt Zujalovic ◽

Benjamin Mayer ◽

Steffen Walter ◽

Sascha Gruss ◽

Ronald Stitz ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Univariate Analysis ◽

Pain Scale ◽

Surgical Intensive Care Unit ◽

Surgical Intensive Care ◽

Flexion Reflex ◽

Nociceptive Flexion Reflex ◽

Behavioral Pain Scale ◽

Reflex Threshold

Abstract Background Pain detection and treatment is a major challenge in the care of critically ill patients. However, in addition to the risk of analgesic undersupply, there is also the risk of overanalgesia. In the perioperative context, the measurement of the nociceptive flexion reflex threshold has become established for measuring the level of analgesia. To date, however, it is unclear whether measurement of NFRT can be usefully applied to noncommunicating, ventilated, and analgosedated ICU patients. Therefore, the aim of the present study was to investigate whether NFRT measurement correlates with the Behavioral Pain Scale (BPS) in critically ill, analgosedated, and mechanically ventilated patients and whether it can also detect possible overanalgesia.Methods In this prospective, observational, single-center study, 114 patients were included. All patients were admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany. First measurements of the NFRT and the Behavioral Pain Scale (BPS) were conducted within 12 hours after admission. In the further observation period, a structured pain assessment was performed at least twice daily until extubation (Group A: BPS + NFRT, Group B: BPS). Univariate analysis was performed to evaluate possible associations between NFRT measurement and baseline characteristics. Furthermore, mixed linear regression modeling was used to evaluate possible effects of administered analgesics or sedatives on NFRT. Results NFRT correlates negatively with the Behavioral Pain Scale. NFRT was almost twice as high in patients with a RASS of -5 compared with patients with a RASS ≥ -4 (RASS -5 - NFRT: 59.40 vs. RASS -4 - NFRT: 29.00, p < 0.001). By means of NFRT measurement, potential overanalgesia could not be detected.Conclusion The NFRT measurement reliably correlates negatively with the Behavioral Pain Scale in critically ill patients. In patients with RASS scores ≤ -4, in whom analgesia level is often difficult to assess, NFRT measurement provides guidance in the assessment of nociceptive processes. However, in order to detect possible overanalgesia and to derive therapeutic consequences, a defined stimulus threshold must be determined for the critically ill patient, above which the absence of pain can be safely assumed.Trial Registration Retrospectively registered at 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

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

10.21203/rs.2.23128/v2 ◽

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

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

BMC Anesthesiology ◽

10.1186/s12871-020-01204-6 ◽

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.

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Is the heart rate variability monitoring using the analgesia nociception index a predictor of illness severity and mortality in critically ill patients with COVID-19? A pilot study

PLoS ONE ◽

10.1371/journal.pone.0249128 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0249128

Author(s):

Cristian Aragón-Benedí ◽

Pablo Oliver-Forniés ◽

Felice Galluccio ◽

Ece Yamak Altinpulluk ◽

Tolga Ergonenc ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Nervous System ◽

Pilot Study ◽

Critically Ill ◽

Critically Ill Patients ◽

High Frequency Component ◽

Surgical Intensive Care Unit ◽

Surgical Intensive Care ◽

Limit Value

Introduction The analysis of heart rate variability (HRV) has proven to be an important tool for the management of autonomous nerve system in both surgical and critically ill patients. We conducted this study to show the different spectral frequency and time domain parameters of HRV as a prospective predictor for critically ill patients, and in particular for COVID-19 patients who are on mechanical ventilation. The hypothesis is that most severely ill COVID-19 patients have a depletion of the sympathetic nervous system and a predominance of parasympathetic activity reflecting the remaining compensatory anti-inflammatory response. Materials and methods A single-center, prospective, observational pilot study which included COVID-19 patients admitted to the Surgical Intensive Care Unit was conducted. The normalized high-frequency component (HFnu), i.e. ANIm, and the standard deviation of RR intervals (SDNN), i.e. Energy, were recorded using the analgesia nociception index monitor (ANI). To estimate the severity and mortality we used the SOFA score and the date of discharge or date of death. Results A total of fourteen patients were finally included in the study. ANIm were higher in the non-survivor group (p = 0.003) and were correlated with higher IL-6 levels (p = 0.020). Energy was inversely correlated with SOFA (p = 0.039) and fewer survival days (p = 0.046). A limit value at 80 of ANIm, predicted mortalities with a sensitivity of 100% and specificity of 85.7%. In the case of Energy, a limit value of 0.41 ms predicted mortality with all predictive values of 71.4%. Conclusion A low autonomic nervous system activity, i.e. low SDNN or Energy, and a predominance of the parasympathetic system, i.e. low HFnu or ANIm, due to the sympathetic depletion in COVID-19 patients are associated with a worse prognosis, higher mortality, and higher IL-6 levels.

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

10.21203/rs.2.23128/v3 ◽

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

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

10.21203/rs.2.23128/v5 ◽

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

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

10.21203/rs.2.23128/v4 ◽

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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Electroacupuncture Improves Gastric Emptying in Critically Ill Neurosurgical Patients: A Pilot Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/1892161 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Man-Ling Kao ◽

Yao-Li Chen ◽

Shu-Ching Lee ◽

Sung-Yen Huang ◽

Ping-Yi Lin

Keyword(s):

Gastric Emptying ◽

Pilot Study ◽

Critically Ill ◽

Surgical Intensive Care Unit ◽

Control Group ◽

Residual Volume ◽

Surgical Intensive Care ◽

Mechanically Ventilated ◽

Neurosurgical Patients ◽

Experimental Group

Objective. To compare the efficacy of combined electroacupuncture and metoclopramide treatment with that of metoclopramide only in improving gastric emptying in critically ill neurosurgical patients.Methods. In this prospective case-control pilot study, a total of 16 adult critically ill mechanically ventilated patients who were treated in the surgical intensive care unit were enrolled. Electrical stimulation was applied to 4 pairs of points (maximum intensity < 9.8 mA at 2 Hz). Patients in the control group received standard treatment with intravenous metoclopramide only. Patients in the experimental group received intravenous metoclopramide plus electroacupuncture treatment once daily for 6 consecutive days.Results. Gastric residual volume in the experimental group (n=7) reduced gradually until the fourth day after treatment with electroacupuncture combined with routine metoclopramide administration. Beginning on the fourth day, residual volume was maintained at less than 200 ml per day for the following two days. In the control group (n=9), there was a gradual reduction in residual volume during the first four days followed by a rebounding increase over the next two days.Conclusions. Electroacupuncture combined with intravenous metoclopramide is a more effective treatment for gastric emptying than metoclopramide alone in adult critically ill patients with impaired brain function.

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Music experience is associated with lower depression level and higher quality of life among family caregivers of critically ill patients

Psychology of Music ◽

10.1177/0305735620906881 ◽

2020 ◽

pp. 030573562090688

Author(s):

Ga Eul Yoo ◽

Jeongmin Kim ◽

Da In Choi ◽

Myung Sun Yeo ◽

Soo Ji Kim ◽

...

Keyword(s):

Quality Of Life ◽

Family Caregivers ◽

Critically Ill ◽

Psychological Health ◽

Critically Ill Patients ◽

University Hospital ◽

Surgical Intensive Care Unit ◽

Surgical Intensive Care ◽

Icu Patients

This study aimed to investigate level of the psychological health of family caregivers of critically ill patients, considering quality of life and depression, and whether it varied depending on their individualized music use. A survey was administered in a surgical intensive care unit (ICU) of a university hospital. Adult family caregivers of ICU patients older than 18 years of age were included. Depression and quality of life were measured via self-administered scales, and emotional states were evaluated using a visual analog scale. Music use in daily life was also queried. A total of 195 caregivers (mean age, 51.2 years) participated in this study (spouses 44.6%, offspring 51.3%, and parents 4.1%). Among respondents, 44.6% were at high risk of depression, and 18.0% of these respondents reported their quality of life as poor or very poor. In terms of singing in their everyday lives, respondents who had singing experience reported higher quality of life and lower depression than those without singing experience. The results of this study support the active engagement in music as resource for caregivers of ICU patients to alleviate their emotional distress. Further investigation into diversified music use and music intervention in critical care should focus on the inclusion of family caregivers.

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

10.21203/rs.2.23128/v6 ◽

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 BackgroundUp 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.MethodsIn 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.ResultsAbout 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.ConclusionLongitudinal 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 registrationRetrospectively registered at German Clinical Trials Register, registration number DRKS 00020542, date of registration: January 27, 2020

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