Kirsten Møller

Rigshospitalet | rigshospitalet · Department of Neuroanaesthesiology

Coma is a medical and socioeconomic emergency. Although underfunded, research on coma and disorders of consciousness has made impressive progress. Lesion-network-mapping studies have delineated the precise brainstem regions that consistently produce coma when damaged. Functional neuroimaging has revealed how mechanisms like “communication through c...

Background: Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with...

Functional MRI (fMRI) and EEG may reveal residual consciousness in patients with disorders of consciousness (DoC), as reflected by a rapidly expanding literature on chronic DoC. However, acute DoC is rarely investigated, although identifying residual consciousness is key to clinical decision-making in the intensive care unit (ICU). Therefore, the o...

Dynamic cerebral autoregulation is often assessed by continuously recorded arterial blood pressure (ABP) and transcranial Doppler-derived mean cerebral blood flow velocity followed by analysis in the time and frequency domain, respectively. Sequential correlation (in the time domain, yielding e.g., the measure mean flow index, Mxa) and transfer fun...

Denmark has experienced an increase in the proportion of invasive vancomycin‐resistant E. faecium (VRE) since 2002 (e.g. <4% in 2015, 7.1% in 2017, and 12% in 2018). At Rigshospitalet we employ active screening at departments with high prevalence or in case of outbreaks. This includes the collection of rectal swabs specifically for VRE screening. O...

Aims Resuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose after hospital arrival are at high risk of mortality due to anoxic brain injury. MicroRNA are small–non-coding RNA molecules ultimately involved in gene-silencing. They show promise as biomarkers, as they are stable in body fluids. The microRNA 9-3p (miR-9-3p) is a...

Objective Invasively measured arterial blood pressure (ABP) is associated with complications, while non-invasively measured ABP is generally considered risk-free. This study aimed to investigate the reliability of non-invasive ABP measured using finger-cuff volume-clamp device compared to invasive ABP measured by an arterial catheter in patients wi...

Background Sevoflurane and propofol are commonly used drugs in general anaesthesia. However, their effects on perioperative immune function are incompletely understood. We hypothesised that sevoflurane and propofol differentially affect immune function in healthy individuals. Therefore, we investigated the effect of sevoflurane and propofol on neut...

Aim: An increasing number of children undergo magnetic resonance imaging requiring anaesthesia or sedation to ensure their immobility; however, magnetic resonance imaging may increase body temperature whereas sedation or anesthesia may decrease it. We investigated changes in body temperature in children who underwent sedation or anesthesia for mag...

Introduction In the early phase after severe brain injury, patients are often bedridden in an attempt to control intracranial homeostasis; however, prolonged immobilisation may trigger complications. There is limited knowledge about the physiological effects of mobilisation in this early phase. Objective To investigate changes in brain tissue oxyg...

Dynamic cerebral autoregulation to spontaneous fluctuations in cerebral perfusion pressure (CPP) is often assessed by transcranial Doppler (TCD) in the time domain, yielding primarily the mean flow index (Mx), or in the frequency domain using transfer function analysis (TFA), yielding gain and phase. For both domains, the measurement of blood press...

Background: Ventriculostomy-related infection (VRI) is a common complication in patients with traumatic brain injury (TBI) treated with an external ventricular drain (EVD). The aim of this study was to investigate incidence and characteristics of patients with VRI, and to explore diagnostic criteria to confidently rule out VRI in patients with TBI...

Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This study aimed to investigate how broad- and narrow-spectrum antibiotics affect the gut microbiome and the resistome in antibiotic naïve patients during neurointensive care. Patients...

Non-culture-based biomarkers may improve diagnosis and antifungal treatment (AFT) of invasive candidiasis (IC). We evaluated an antifungal stewardship programme (AFSP) in a prospective intensive care unit (ICU) study, which included T2Candida and Candida mannan antigen (MAg) screening of patients with sepsis and a high risk of IC. Patients with non...

Introduction Intensive care for patients with severe acute brain injury aims both to treat the immediate consequences of the injury and to prevent and treat secondary brain injury to ensure a good functional outcome. Sedation may be used to facilitate mechanical ventilation, for treating agitation, and for controlling intracranial pressure. Ketamin...

Background Early mobilization on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomized clinical trials are lacking. This detailed statistical analysis plan describes the analyses of data collected in a randomized clinical feasibility trial for early mobilization by head-up...

Cerebral autoregulation is a complex mechanism that serves to keep cerebral blood flow relatively constant within a wide range of cerebral perfusion pressures. The mean flow index (Mx) is one of several methods to assess dynamic cerebral autoregulation, but its reliability and validity have never been assessed systematically. The purpose of the pre...

In patients with severe traumatic brain injury, there is limited evidence of the clinical effect of early orthostatic exercise, although such exercise may strengthen systemic or cerebral hemodynamic responses to head-up tilt, thereby minimizing orthostatic intolerance. We measured dynamic cerebral autoregulation (dCA) and the occurrence of orthosta...

Brain abscesses are often polymicrobial and of unclear primary origin. Here we compare the use of Next Generation Sequencing (NGS) technology with classical microbiological diagnostics for identification of clinically relevant microorganisms and describe the microbiome profiling with respect to the primary source of brain abscess. Thirty‐six sample...

Introduction Hypophosphataemia is common in critically ill patients, but neither its prevalence nor its association with outcome have been investigated specifically in patients with aneurysmal subarachnoid haemorrhage (aSAH). Methods Patients with aSAH and at least one phosphate measurement were included from two independent cohorts; An American c...

Objective In critical care, continuous EEG (cEEG) monitoring is useful for delirium diagnosis. Although visual cEEG analysis is most commonly used, automatic cEEG analysis has shown promising results in small samples. Here we aimed to compare visual versus automatic cEEG analysis for delirium diagnosis in septic patients. Methods We obtained cEEG...

Background: Mean flow index (Mxa) for evaluating dynamic cerebral autoregulation is derived using varying approaches for calculation, which may explain that the reliability ranges from poor to excellent. The comparability, repeatability, stability, and internal consistency of approaches have not previously been assessed. Methods: We included 60...

Introduction Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials....

Background: Intensive rehabilitation of patients after severe traumatic brain injury aims to improve functional outcome. The effect of initiating rehabilitation in the early phase, in the form of head-up mobilization, is unclear. Objective: To assess whether early mobilization is feasible and safe in patients with traumatic brain injury admitted to...

Intro: Early Brain Injury (EBI) after non-traumatic subarachnoid hemorrhage (SAH) is a significant mediator of neurological injury, but the injury pathways and markers are not well understood. We hypothesized that the inflammatory mediator soluble ST2 (sST2) is associated with markers of EBI. Methods: We studied two independent cohorts, including 1...

Background: The complement system has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients. Methods: This observational, explorative cohort study included 92 ALS p...

Background: Due to an expected surge of COVID-19 patients in need of mechanical ventilation, the intensive care capacity was doubled at Rigshospitalet, Copenhagen, in March 2020. This resulted in an urgent need for doctors with competence in working with critically ill COVID-19 patients. A training course and a theoretical test for non-intensivist...

The transcranial Doppler ultrasound-derived mean flow index (Mxa) is widely used for assessing dynamic cerebral autoregulation (dCA) in different clinical populations. This study aimed at estimating the relative and absolute reliability of Mxa in healthy participants in the supine position and during head-up tilt (HUT). Fourteen healthy participant...

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) reportedly elevates arterial blood pressure (ABP) during non-traumatic cardiac arrest. Objectives This randomized, blinded trial of cardiac arrest in pigs evaluated the effect of automated REBOA two minutes after balloon inflation on ABP (primary endpoint) as well as arte...

This study evaluated microRNA (miRNA) changes in cerebrospinal fluid (CSF) and their association with the occurrence of delayed cerebral ischemia (DCI) and poor functional outcome after SAH. Forty-three selected miRNAs were measured in daily CSF samples from a discovery cohort of SAH patients admitted to Rigshospitalet, Copenhagen, Denmark, and com...

Background This exploratory study investigated the time-course of lectin complement pathway (LCP) initiators in cerebrospinal fluid (CSF) and plasma in patients with subarachnoid hemorrhage (SAH), as well as their relationship to delayed cerebral ischemia (DCI) and functional outcome. Methods Concentrations of ficolin-1, ficolin-2, ficolin-3, and...

Background: Although used extensively worldwide, the effects of general anaesthesia on the human brain remain largely elusive. Moreover, general anaesthesia may contribute to serious conditions or adverse events such as postoperative cognitive dysfunction and delirium. To understand the basic mechanisms of general anaesthesia, this project aims to...

Background There is increasing focus on earlier rehabilitation in patients with traumatic or hypoxic brain injury or stroke. This systematic review evaluates the benefits and harms of early head-up mobilisation versus standard care in patients with severe acquired brain injury. Methods We searched Medline, CENTRAL, EMBASE, four other databases and...

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a technique where a balloon is advanced through the common femoral artery and temporarily inflated for treatment of cardiac arrest or non-compressible haemorrhage. The aim of this study was to measure intravascular distances relevant for correct placement of the REBOA catheter usi...

Introduction Amyotrophic lateral sclerosis (ALS) is a devastating, progressive disease that causes degeneration of the motor neurons leading to paresis of the bulbar and the skeletal musculature. The pathogenesis of ALS remains unknown. We will test the hypothesis that the complement system is involved in the pathophysiology of ALS. This protocol a...

IntroductionThe Glasgow Coma Scale (GCS) and visual inspection of pupillary function are routine measures to monitor patients with impaired consciousness and predict their outcome in the neurointensive care unit (neuro-ICU). Our aim was to compare more recent measures, i.e. FOUR score and automated pupillometry, to standard monitoring with the GCS...

Background Cognitive impairment and reduced health‐related quality of life (HRQoL) are well established sequelae of critical illness. Studies on survivors of critical illness have found delirium to be a predictor of these conditions, but evidence regarding survivors of acute brain injury is sparse. We aimed to explore if delirium duration was assoc...

Background Hypozincaemia may develop in critically ill patients, including those with acute brain injury in the early phase after hospital admission. The aim of this study was to investigate the prevalence of hypozincaemia after aneurysmal subarachnoid haemorrhage (aSAH) and its association with delayed cerebral ischemia and functional outcome.Meth...

New findings: What is the central question of this study? Can the change in haemoglobin's affinity for oxygen in the human cerebral circulation be modelled in vivo? What is the main finding and its importance? We provide a novel method for modelling the oxyhaemoglobin dissociation curve at the cerebral capillary level in humans, so that the cerebr...

Background Neurovascular-based imaging techniques such as functional MRI (fMRI) may reveal signs of consciousness in clinically unresponsive patients but are often subject to logistical challenges in the intensive care unit (ICU). Near-infrared spectroscopy (NIRS) is another neurovascular imaging technique but low cost, can be performed serially at...

Objectives: Knowledge regarding delirium prevention in patients with acute brain injury remains limited. We tested the hypothesis that an intervention bundle which targeted sedation, sleep, pain, and mobilisation would reduce delirium in patients with acute brain injury. Design: A prospective before-after intervention study: a five-month phase o...

This work describes a fully-integrated portable microfluidic analysis system for real-time monitoring of dynamic changes in glucose and lactate occurring in the brain as a result of cardiac arrest and resuscitation. Brain metabolites are sampled using FDA-approved microdialysis probes and coupled to a high-temporal resolution 3D printed microfluidi...

Hypoxaemia is present in many critically ill patients, and may contribute to encephalopathy. Changes in the passage of large neutral amino acids (LNAAs) across the blood-brain barrier (BBB) with an increased cerebral influx of aromatic amino acids into the brain may concurrently be present and also contribute to encephalopathy, but it has not been...

Background: Naloxone, an opioid receptor antagonist, is used as a pharmacological tool to detect tonic endogenous activation of opioid receptors in experimental pain models. We describe a pharmacokinetic model linking naloxone pharmacokinetics to its main metabolite after high-dose naloxone infusion. Methods: Eight healthy volunteers received a...

Background: Delayed cerebral ischemia (DCI) is a serious and frequent complication following subarachnoid hemorrhage (SAH). The pathophysiology behind DCI remains poorly understood, but inflammation has been proposed to play a significant role. This study investigated the relationship between plasma levels of some of the most important inflammator...

The purpose of this review is to increase the knowledge about diagnosis and treatment of aneurysmal subarachnoid haemorrhage (aSAH), which is an infrequent and critical condition with a high risk of severe morbidity and mortality. The outcome is improved by correct and efficient diagnosis and early treatment, including aneurysm repair. General prac...

Objective: To investigate whether soluble ST2, a prognostic marker in cardiovascular and inflammatory disorders, is associated with neurological injury after aneurysmal subarachnoid hemorrhage (SAH). Methods: We studied SAH patients from two independent cohorts. Outcome assessments included functional status at 90 days using the modified Rankin...

Traumatic brain injury (TBI) contributes to almost a third of all trauma related deaths and those that survive often suffer from long term physical and cognitive deficits. Ciclosporin has shown promising neuroprotective properties in preclinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety pr...

Introduction: Delayed cerebral ischaemia (DCI) is one of the most frequent complications of aneurysmal subarachnoid haemorrhage (aSAH). The purpose of the present retrospective cohort study of patients with aSAH was to identify the association between DCI, functional outcome and 4-year mortality. Methods: Patients admitted to the Neurointensive...

Developing positron emission tomography (PET) radioligands for the detection of endogenous serotonin release will enable the investigation of serotonergic deficits in many neuropsychiatric disorders. The present study investigates how acute challenges that aim to increase or decrease cerebral serotonin levels affect binding of the serotonin 2A rece...

Background Delirium is common during sepsis, although under-recognized. We aimed to assess the value of continuous electroencephalography (cEEG) to aid in the diagnosis of delirium in septic patients. Methods We prospectively evaluated 102 consecutive patients in a medical intensive care unit (ICU), who had sepsis or septic shock, without evidence...

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) has a lower incidence than ischemic stroke but affects younger individuals with a high mortality and a high frequency of complications in survivors. The underlying pathways that contribute to poor functional outcome are poorly understood. Hypothesis: MicroRNA (miRNA) changes in cerebrospinal fl...

Hospitals worldwide are working on minimizing unnecessary use of antimicrobials. To assess actual changes of antimicrobial usage, correct and precise measurements are necessary. This study aimed to compare data on the purchase of antibiotics from the pharmacy and the administration of antibiotics to patients, respectively, in an intensive care unit...

Background Because osmotic fluid shifts may occur over the blood‐brain barrier, patients with acute brain injury are theoretically at risk of surges in intracranial pressure (ICP) during hemodialysis. However, this remains poorly investigated. We studied changes in ICP during hemodialysis in such patients. Methods We performed a retrospective stud...

Aims and Objectives: To facilitate individualized assessment of unresponsive patients in the intensive care unit for signs of preserved consciousness after acute brain injury. Background: Physicians and neuroscientists are increasingly recognizing a disturbing dilemma: Brain-injured patients who appear entirely unresponsive at the bedside may show...

Background: Intensive rehabilitation of patients with severe traumatic brain injury is generally applied in the subacute stages of the hospital stay. Few studies have assessed the association between early and intensive physical rehabilitation and functional outcomes. The aim of this trial is to assess the feasibility of an intensive physical rehab...

Background Delirium is underinvestigated in the neuro‐critically ill, although the harmful effect of delirium is well established in patients in medical and surgical intensive care units (ICU).To detect delirium, a valid tool is needed. We hypothesized that delirium screening would be feasible in patients with acute brain injury and we aimed to val...

Amyotrophic lateral sclerosis (ALS) is a devastating, neurodegenerative motor neuron disease. The aetiology of ALS remains an enigma which hinders the design of an effective treatment to prevent, postpone, or reverse the pathophysiological changes occurring during the aggressive progression of this disease. During the last decade, basic research wi...

Background: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock. Methods: In th...

The objective of this study was to develop a personalized inflammatory model and estimate subject-specific parameters that could be related to changes in heart rate variability (HRV), a measure that can be obtained non-invasively in real time. An inflammatory model was developed and calibrated to measurements of interleukin-6 (IL-6), tumor necrosis...

The systemic inflammatory response triggered by lipopolysaccharide (LPS) is associated with cerebral vasoconstriction, but the underlying mechanisms are unknown. We therefore examined whether a four-hour intravenous LPS infusion (0.3 ng kg^-1) induces any changes in the transcerebral net exchange of the vasoactive peptides endothelin-1 (E...

Objectives To assess the value of continuous electroencephalography (cEEG) in detecting delirium in a medical intensive care unit (ICU), applying a visual, qualitative analysis in accordance with The American Clinical Neurophysiology Society’s Standardized Critical Care Terminology. Methods Single-center prospective observational study including 1...

We reassessed data from a previous study on the transcerebral net exchange of large neutral amino acids (LNAAs) using a novel mathematical model of blood–brain barrier (BBB) transport. The study included twelve healthy volunteers who received a 4-h intravenous lipopolysaccharide (LPS) infusion (total dose: 0·3 ng/kg), a human experimental model of...

Background and purpose: Delayed cerebral ischemia (DCI) accounts for a major part of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia. This study compared miRNA profiles in cerebrospinal fluid from neurologically healthy patients, as well as...

Background: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased 90-day mortality with hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate. To explore the underlying pathophysiology, we compared early changes in plasma cytokine concentrations between patients resuscitated with HES vs. Ringer's acetate. Methods:...

Background: Assessment of the default mode network (DMN) using resting-state functional magnetic resonance imaging (fMRI) may improve assessment of the level of consciousness in chronic brain injury, and therefore, fMRI may also have prognostic value in acute brain injury. However, fMRI is much more challenging in critically ill patients because o...