A pragmatic approach to intravenous anaesthetics and electroencephalographic endpoints for the treatment of refractory and super-refractory status epilepticus in critical care.

Status epilepticus is a common neurological emergency, with overall mortality around 20%. Over half of cases are first time presentations of seizures. The pathological process by which spontaneous seizures are generated arises from an imbalance in excitatory and inhibitory neuronal networks, which if unchecked, can result in alterations in intracellular signalling pathways and electrolyte shifts, which bring about changes in the blood brain barrier, neuronal cell death and eventually cerebral atrophy. This narrative review focusses on the treatment of status epilepticus in adults. Anaesthetic agents interrupt neuronal activity by enhancing inhibitory or decreasing excitatory transmission, primarily via GABA and NMDA receptors. Intravenous anaesthetic agents are commonly used as second or third line drugs in the treatment of refractory status epilepticus, but the optimal timing and choice of anaesthetic drug has not yet been established by high quality evidence. Titration of antiepileptic and anaesthetic drugs in critically ill patients presents a particular challenge, due to alterations in drug absorbtion and metabolism as well as changes in drug distrubution, which arise from fluid shifts and altered protein binding. Furthermore, side effects associated with prolonged infusions of anaesthetic drugs can lead to multi-organ dysfunction and a need for critical care support. Electroencelography can identify patterns of burst suppression, which may be a target to guide weaning of intravenous therapy. Continuous elctroencephalography has the potential to directly impact clinical care, but despite its utility, major barriers exist which have limited its widespread use in clinical practice. A flow chart outlining the timing and dosage of anaesthetic agents used at our institution is provided.

New-onset super refractory status epilepticus: A case-series.

INTRODUCTION: Literature on New-Onset Refractory Status Epilepticus (NORSE) is scarce and management is guided mainly by retrospective reports, short case series or expert opinions. We aimed to add to the pool of the available data by retrospectively reviewing seven cases of NORSE cases admitted to our hospital over the last five years between January 2014 and March 2019. METHODS: Fully anonymised data from medical charts, EEG reports, imaging reports, laboratory test results, types of antiepileptic medications, intravenous anaesthetic therapy, and immune therapies received was collected, along with response to treatment, length of hospital stay and outcome at discharge. RESULTS: The mean age was 43.5 ±â€¯23.8 years (range 18-75) and three patients were females. Prodromal symptoms consisted mainly of fever (4/7), headache (4/7) and self terminating seizures (7/7), before presenting with status epilepticus. Initial imaging findings were abnormal in 3/7 and CSF analysis in 3/7. All patients underwent intermittent EEG recordings, mainly for titration or tapering of the anaesthetic agents, with the initial goal of achieving burst suppression and cessation of electrographic seizures. Our index case spent the longest time in therapeutic burst suppression (102 days) and remained on thiopentone for 214 days. The mean duration of NICU stay was 88 ±â€¯85.4 days (range 4-225 days) while the mean duration of hospital stay was 113.8 ±â€¯111.2 days (range 17-292). CONCLUSIONS: The management of patients with NORSE remains challenging, often requiring multiple intravenous anaesthetic treatments, leading to complicated and prolonged hospital and intensive care unit stays but good outcome remains possible.

Co-trimoxazole-induced hypoglycaemia in an immunosuppressed intensive care patient.

An 18-year-old female inpatient on a neurosciences intensive care unitwith new onset super-refractory epilepsy became hypoglycaemic 48 h after commencing co-trimoxazole. She had been placed on this for prophylaxis against Pneumocystis jiroveci infection in the context of significant immunosuppression with high-dose corticosteroid therapy. In order to maintain glucose control, she required a continuous infusion of 10% dextrose at rates of 15-25 ml/h. Recurrent attempts to wean this were limited by further hypoglycaemia, until she spontaneously regained normoglycaemia after 73 days. This case report will discuss this unusual case of refractory hypoglycaemia, and the proposed pathophysiology of hypoglycaemia related to co-trimoxazole therapy.

Opioid suppression of conditioned anticipatory brain responses to breathlessness.

Opioid painkillers are a promising treatment for chronic breathlessness, but are associated with potentially fatal side effects. In the treatment of breathlessness, their mechanisms of action are unclear. A better understanding might help to identify safer alternatives. Learned associations between previously neutral stimuli (e.g. stairs) and repeated breathlessness induce an anticipatory threat response that may worsen breathlessness, contributing to the downward spiral of decline seen in clinical populations. As opioids are known to influence associative learning, we hypothesized that they may interfere with the brain processes underlying a conditioned anticipatory response to breathlessness in relevant brain areas, including the amygdala and the hippocampus. Healthy volunteers viewed visual cues (neutral stimuli) immediately before induction of experimental breathlessness with inspiratory resistive loading. Thus, an association was formed between the cue and breathlessness. Subsequently, this paradigm was repeated in two identical neuroimaging sessions with intravenous infusions of either low-dose remifentanil (0.7ng/ml target-controlled infusion) or saline (randomised). During saline infusion, breathlessness anticipation activated the right anterior insula and the adjacent operculum. Breathlessness was associated with activity in a network including the insula, operculum, dorsolateral prefrontal cortex, anterior cingulate cortex and the primary sensory and motor cortices. Remifentanil reduced breathlessness unpleasantness but not breathlessness intensity. Remifentanil depressed anticipatory activity in the amygdala and the hippocampus that correlated with reductions in breathlessness unpleasantness. During breathlessness, remifentanil decreased activity in the anterior insula, anterior cingulate cortex and sensory motor cortices. Remifentanil-induced reduction in breathlessness unpleasantness was associated with increased activity in the rostral anterior cingulate cortex and nucleus accumbens, components of the endogenous opioid system known to decrease the perception of aversive stimuli. These findings suggest that in addition to effects on brainstem respiratory control, opioids palliate breathlessness through an interplay of altered associative learning mechanisms. These mechanisms provide potential targets for novel ways to develop and assess treatments for chronic breathlessness.

Capillary blood gases in acute exacerbations of COPD.

OBJECTIVES: To assess the correlation and agreement between measurements of PO(2), PCO(2), H(+) and HCO(3)(-) in arterial and capillary blood in patients with acute exacerbations of COPD. To assess the repeatability of capillary measurements. DESIGN: Method comparison study. SETTING: Accident and emergency department in a university teaching hospital. MAIN OUTCOME MEASURES: Measurements of PO(2), PCO(2), H(+) and HCO(3)(-) in one arterial and two capillary samples taken from consecutive patients with acute exacerbations of COPD. RESULTS: The agreement between measurements of PCO(2), H(+) and HCO(3)(-) in arterial and capillary blood was good with mean differences of 0.087 kPa, 1.044 nmol/l and 0.513 mmol/l, respectively. The corresponding 95% limits of agreement were narrow. The agreement between measurements of PO(2) was poor with a mean difference of 1.256 kPa and wide 95% limits of agreement. There was good repeatability between capillary samples with mean differences of 0.094 kPa, 0.674 nmol/l and 0.028 mmol/l for measurements of PCO(2), H(+) and HCO(3) respectively and narrow coefficients of repeatability. CONCLUSIONS: Capillary blood gas measurements provide an accurate assessment of PCO(2), H(+) and HCO(3)(-) and can be used to reliably measure the ventilatory status of patients. Combined with continuous pulse oximetry they can be used as an alternative to arterial blood gas measurements in patients with acute exacerbations of COPD.