High-flow via a tracheostomy tube and speaking valve during weaning from mechanical ventilation and tracheostomy.

BACKGROUND: Weaning from mechanical ventilation and tracheostomy after prolonged intensive care consume enormous resources with optimal management not currently well described. Restoration of respiratory flow via the upper airway is essential and early cuff-deflation using a one-way valve (OWV) is recommended. However, extended OWV use may cause dry airways and thickened secretions which challenge the weaning process. High-flow therapy via the tracheostomy tube (HFT-T) humidifies inspired air and may be connected via an in-line OWV (HFT-T-OWV) alleviating these problems. We aim to provide clinical and experimental data on the safety of HFT-T-OWV along with a practical guide to facilitate clinical use during weaning from mechanical ventilation and tracheostomy. METHODS: Data on adverse events of HFT-T-OWV were retrieved from a quality register for patients treated at an intensive care rehabilitation center between 2019 and 2022. Benchtop experiments were performed to measure maximum pressures and pressure support generated by HFT-T-OWV at 25-60 L/min flow using two different HFT-T adapters (interfaces). In simulated airway obstruction using a standard OWV (not in-line) maximum pressures were measured with oxygen delivered via the side port at 1-3 L/min. RESULTS: Of 128 tracheostomized patients who underwent weaning attempts, 124 were treated with HFT-T-OWV. The therapy was well tolerated, and no adverse events related to the practice were detected. The main reason for not using HFT-T-OWV was partial upper airway obstruction using a OWV. Benchtop experiments demonstrated HFT-T-OWV maximum pressures <4 cmH2 O and pressure support 0-0.6 cmH2 O. In contrast, 1-3 L/min supplemental oxygen via a standard OWV caused pressures between 84 and 148 cmH2 O during simulated airway obstruction. CONCLUSIONS: Current study clinical data and benchtop experiments indicate that HFT-T-OWV was well tolerated and appeared safe. Pressure support was low, but humidification may enable extended use of a OWV without dry airway mucosa and thickened secretions. Results suggest the treatment could offer advantages to standard OWV use, with or without supplementary oxygen, as well as to HFT-T without a OWV, for weaning from mechanical ventilation and tracheostomy. However, for definitive treatment recommendations, randomized clinical trials are needed.

Outcomes of prolonged intensive care and rehabilitation at a specialized multidisciplinary center in Sweden.

BACKGROUND: Specialized clinics may improve the outcome for patients with prolonged intensive care stays. Admission may depend on diagnosis, need of respiratory support and more. We report the results from a Swedish specialized center with a multidisciplinary team approach to continued intensive care and simultaneous rehabilitation regardless of patients' primary diagnosis or ventilator need. METHODS: All patients admitted and discharged from 2015 to 2018 were included. Demographics, diagnoses, ventilatory support requirement, discharge destination and survival were retrieved from the center´s quality registry. RESULTS: A total of 181 patients, mean age 61 ± 16 years, 64% men, were analyzed. A neurological diagnosis was the cause for hospitalization in 46% of patients. Of the 55 patients admitted to the center for weaning from mechanical ventilation, 89% were successfully weaned within a median of 25 (interquartile range (IQR) 16-45) days. Decannulation was intended in 117 patients of which 90% were successful within a median of 25 (IQR 13-43) days. Readmission to intensive care was 4%. Most patients were discharged to their home or to rehabilitation clinics with a lower level of care. In-clinic mortality was 3%. Survival beyond 1 and 2 years after discharge was 79% and 70%, respectively. CONCLUSION: Patients with prolonged intensive care and complex medical needs treated at a specialized center in Sweden had weaning and decannulation rates comparable to or better than previously reported. Mortality was low, and most patients were discharged home or for further rehabilitation. This was achieved with a multidisciplinary team approach to continued intensive care and simultaneous rehabilitation.

Lack of clinically relevant correlation between subjective and objective cognitive function in ICU survivors: a prospective 12-month follow-up study.

BACKGROUND: Cognitive impairment and psychological distress are common in intensive care unit (ICU) survivors. Early identification of affected individuals is important, so intervention and treatment can be utilized at an early stage. Cognitive Failures Questionnaire (CFQ) is commonly used to screen for subjective cognitive function, but it is unclear whether CFQ scores correlate to objective cognitive function in this population. METHODS: Between 2014 and 2018, 100 ICU survivors aged 18-70 years from the general ICU at the Karolinska University Hospital, Solna, were included in the study. Out of these, 58 patients completed follow-up at 3 months after ICU discharge, 51 at 6 months, and 45 at 12 months. Follow-up included objective cognitive function testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and subjective cognitive function testing with the self-rating Cognitive Failures Questionnaire (CFQ), as well as psychological self-rating with the Post-Traumatic Stress Symptoms Scale-10 (PTSS-10) and Hospital Anxiety and Depression Scale (HADS). RESULTS: The prevalence of cognitive impairment as measured by four selected CANTAB tests was 34% at 3 months after discharge, 18% at 6 months, and 16% at 12 months. There was a lack of significant correlation between CANTAB scores and CFQ scores at 3 months (r = - 0.134-0.207, p > 0.05), at 6 months (r = - 0.106-0.257, p > 0.05), and at 12 months after discharge (r = - 0.070-0.109, p > 0.05). Correlations between CFQ and PTSS-10 scores and HADS scores, respectively, were significant over the follow-up period (r = 0.372-0.710, p ≤ 0.001-0.023). In contrast, CANTAB test scores showed a weak correlation with PTSS-10 and HADS scores, respectively, at 3 months only (r = - 0.319-0.348, p = 0.008-0.015). CONCLUSION: We found no clinically relevant correlation between subjective and objective cognitive function in this cohort of ICU survivors, while subjective cognitive function correlated significantly with psychological symptoms throughout the follow-up period. Treatment and evaluation of ICU survivors' recovery need to consider both subjective and objective aspects of cognitive impairment, and subjective reports must be interpreted with caution as an indicator of objective cognitive function.

Neural Control of Inflammation: Implications for Perioperative and Critical Care.

Inflammation and immunity are regulated by neural reflexes. Recent basic science research has demonstrated that a neural reflex, termed the inflammatory reflex, modulates systemic and regional inflammation in a multiplicity of clinical conditions encountered in perioperative medicine and critical care. In this review, the authors describe the anatomic and physiologic basis of the inflammatory reflex and review the evidence implicating this pathway in the modulation of sepsis, ventilator-induced lung injury, postoperative cognitive dysfunction, myocardial ischemia-reperfusion injury, and traumatic hemorrhage. The authors conclude with a discussion of how these new insights might spawn novel therapeutic strategies for the treatment of inflammatory diseases in the context of perioperative and critical care medicine.

Effects of morphine and midazolam on pharyngeal function, airway protection, and coordination of breathing and swallowing in healthy adults.

BACKGROUND: Drugs used for sedation in anesthesia and intensive care may cause pharyngeal dysfunction and increased risk for aspiration. In this study, the authors investigate the impact of sedative doses of morphine and midazolam on pharyngeal function during swallowing and coordination of breathing and swallowing. METHODS: Pharyngeal function, coordination of breathing and swallowing, and level of sedation were assessed by manometry, videoradiography, measurements of respiratory airflow, and a visual analog scale in 32 healthy volunteers (age 19 to 35 yr). After baseline recordings, morphine (0.1 mg/kg) or midazolam (0.05 mg/kg) was administered intravenously for 20 min, followed by recordings at 10 and 30 min after the end of infusion. RESULTS: Pharyngeal dysfunction, seen as misdirected or incomplete swallowing or penetration of bolus to the airway, increased after morphine infusion to 42 and 44% of swallows compared with 17% in baseline recordings. Midazolam markedly increased incidence of pharyngeal dysfunction from 16 to 48% and 59%. Morphine prolonged apnea before swallowing, and midazolam increased the number of swallows followed by inspiration. CONCLUSION: Morphine and midazolam in dosages that produce sedation are associated with increased incidence of pharyngeal dysfunction and discoordinated breathing and swallowing, a combination impairing airway protection and potentially increasing the risk for pulmonary aspirations.

Human genetic evidence for involvement of CD137 in atherosclerosis.

Atherosclerosis is an inflammatory disease and the main cause of cardiovascular disease. Inflammation promotes plaque instability and clinical disease, such as myocardial infarction, stroke and peripheral vascular disease. Subclinical atherosclerosis begins with thickening of the arterial intimal layer, and increased intima-media thickness (IMT) in the carotid artery is a widely used measurement of subclinical atherosclerosis. Activation of CD137 (tumor necrosis factor receptor super family 9) promotes inflammation and disease development in murine atherosclerosis. CD137 is expressed in human atherosclerosis, but its role is largely unknown. This study uses a genetic approach to investigate CD137 in human atherosclerotic disease. In publicly available data on genotype and gene expression from the HapMap project, the minor T allele of rs2453021, a single nucleotide polymorphism in CD137, was significantly associated with CD137 gene expression. In the PROCARDIS and Wellcome Trust Case Control Consortium (WTCCC) cohorts of 13,029 cases and controls, no significant association was detected between the minor T allele of rs2453021 and risk for coronary artery disease or myocardial infarction. However, in the IMPROVE multicenter study of 3,418 individuals, the minor T allele of rs2453021 was associated with increased IMT of the common carotid artery (CCA), as measured by ultrasonography, with presence of plaque in CCA and with increased incidence of adverse noncardiac vascular events. Taken together, this study shows that the minor T allele of rs2453021 is associated with increased IMT in the CCA and increased risk of incident noncardiac vascular events, thus providing the first human genetic evidence for involvement of CD137 in atherosclerosis.

Pharyngeal function and breathing pattern during partial neuromuscular block in the elderly: effects on airway protection.

BACKGROUND: Intact pharyngeal function and coordination of breathing and swallowing are essential for airway protection and to avoid respiratory complications. Postoperative pulmonary complications caused by residual effects of neuromuscular-blocking agents occur more frequently in the elderly. Moreover, elderly have altered pharyngeal function which is associated with increased risk of aspiration. The purpose of this study was to evaluate effects of partial neuromuscular block on pharyngeal function, coordination of breathing and swallowing, and airway protection in individuals older than 65 yr. METHODS: Pharyngeal function and coordination of breathing and swallowing were assessed by manometry and videoradiography in 17 volunteers, mean age 73.5 yr. After control recordings, rocuronium was administered to obtain steady-state train-of-four ratios of 0.70 and 0.80 followed by spontaneous recovery to greater than 0.90. RESULTS: Pharyngeal dysfunction increased significantly at train-of-four ratios 0.70 and 0.80 to 67 and 71%, respectively, compared with 37% at control recordings, and swallowing showed a more severe degree of dysfunction during partial neuromuscular block. After recovery to train-of-four ratio of greater than 0.90, pharyngeal dysfunction was not significantly different from the control state. Resting pressure in the upper esophageal sphincter was lower at all levels of partial neuromuscular block compared with control recordings. The authors were unable to demonstrate impaired coordination of breathing and swallowing. CONCLUSION: Partial neuromuscular block in healthy elderly individuals causes an increased incidence of pharyngeal dysfunction from 37 to 71%, with impaired ability to protect the airway; however, the authors were unable to detect an effect of partial neuromuscular block on coordination of breathing and swallowing.

Neural control of the immune system.

Neural reflexes support homeostasis by modulating the function of organ systems. Recent advances in neuroscience and immunology have revealed that neural reflexes also regulate the immune system. Activation of the vagus nerve modulates leukocyte cytokine production and alleviates experimental shock and autoimmune disease, and recent data have suggested that vagus nerve stimulation can improve symptoms in human rheumatoid arthritis. These discoveries have generated an increased interest in bioelectronic medicine, i.e., therapeutic delivery of electrical impulses that activate nerves to regulate immune system function. Here, we discuss the physiology and potential therapeutic implications of neural immune control.

A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate atherosclerosis.

All-trans retinoic acid, controlled by cytochrome P450, family 26 (CYP26) enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26 subfamily B, polypeptide 1 (CYP26B1) in atherosclerosis and the effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries, and CYP26B1 and the macrophage marker CD68 were colocalized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic arteries than in normal arteries. Databases were queried for nonsynonymous CYP26B1 single nucleotide polymorphisms (SNPs) and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophagelike cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions, as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis.

Co-ordination of spontaneous swallowing with respiratory airflow and diaphragmatic and abdominal muscle activity in healthy adult humans.

Co-ordination of breathing and swallowing is essential for normal pharyngeal function and to protect the airway. To allow for safe passage of a bolus through the pharynx, respiration is interrupted (swallowing apnoea); however, the control of airflow and diaphragmatic activity during swallowing and swallowing apnoea are not fully understood. Here, we validated a new airflow discriminator for detection of respiratory airflow and used it together with diaphragmatic and abdominal electromyography (EMG), spirometry and pharyngeal and oesophageal manometry. Co-ordination of breathing and spontaneous swallowing was examined in six healthy volunteers at rest, during hypercapnia and when breathing at 30 breaths min(-1). The airflow discriminator proved highly reliable and enabled us to determine timing of respiratory airflow unambiguously in relation to pharyngeal and diaphragmatic activity. During swallowing apnoea, the passive expiration of the diaphragm was interrupted by static activity, i.e. an 'active breath holding', which preserved respiratory volume for expiration after swallowing. Abdominal EMG increased throughout pre- and post-swallowing expiration, more so during hyper- than normocapnia, possibly to assist expiratory airflow. In these six volunteers, swallowing was always preceded by expiration, and 93 and 85% of swallows were also followed by expiration in normo- and hypercapnia, respectively, indicating that, in man, swallowing during the expiratory phase of breathing may be even more predominant than previously believed. This co-ordinated pattern of breathing and swallowing potentially reduces the risk for aspiration. Insights from these measurements in healthy volunteers and the airflow discriminator will be used for future studies on airway protection and effects of disease, drugs and ageing.

Sevoflurane anesthesia alters exploratory and anxiety-like behavior in mice lacking the beta2 nicotinic acetylcholine receptor subunit.

BACKGROUND: Preexisting cognitive impairment and advanced age are factors that increase the risk of developing postoperative cognitive dysfunction. Because anesthetic agents interfere with cholinergic transmission and as impairment of cholinergic function is associated with cognitive decline, the authors studied how the volatile anesthetic sevoflurane affects exploratory and anxiety-like behavior in young and aged animals with a genetically modified cholinergic system. METHODS: Young and aged wild-type and mutant mice lacking the beta2 subunit of the nicotinic cholinergic receptor (beta2KO) were anesthetized for 2 h with 2.6% sevoflurane in oxygen and compared with nonanesthetized controls. Locomotor activity and organization of movement in the open field model were assessed before and 24 h after anesthesia. Locomotor activity and anxiety-like behavior in the elevated plus maze were assessed 24 h after anesthesia. High- and low-affinity nicotinic receptor and cholinergic uptake site densities were evaluated in the hippocampus, amygdala, and forebrain regions using receptor autoradiography. RESULTS: Sevoflurane anesthesia significantly reduced locomotor activity, altered temporospatial organization of trajectories, and increased anxiety-like behavior in young beta2KO mice, whereas no such changes were observed in young wild-type mice. Aged wild-type and beta2KO mice displayed reactions that were similar, but not identical, to the reactions of young mice to sevoflurane anesthesia. However, behavioral changes were not associated with differences in nicotinic receptor or cholinergic uptake site densities. CONCLUSION: In conclusion, sevoflurane anesthesia altered exploratory and anxiety-like behavior in mice lacking the beta2 nicotinic acetylcholine receptor subunit.

Neuromuscular block and the electroencephalogram during sevoflurane anaesthesia.

The effect of neuromuscular block on the anaesthetic depth of hypnosis is an elusive question. We simultaneously investigated the influence of neuromuscular block on the bispectral index, a measure of hypnosis during general anaesthesia, and on the electroencephalogram. Patients were anaesthetized with sevoflurane. Noxious tetanic electrical stimulation was applied on two occasions: before and after profound neuromuscular block achieved with rocuronium. Neuromuscular block significantly attenuated the effect from noxious stimulation on electroencephalogram power and synchrony in the gamma band (P<0.05), and the corresponding effect on bispectral index (P<0.02). These findings are probably due to the reduced arousing afferent input from paralysed muscles, and not to changes in the frontal electromyogram.

The effect of neuromuscular block and noxious stimulation on hypnosis monitoring during sevoflurane anesthesia.

BACKGROUND: There are conflicting results on the influence of neuromuscular block (NMB) on the bispectral index (BIS). We investigated the influence of two degrees of NMB on BIS, Alaris auditory-evoked potential index (AAI), and the electromyogram (EMG) obtained with needle electrodes from the frontal and temporal muscles, immediately adjacent to the BIS-sensor. METHODS: Twenty patients were anesthetized with sevoflurane, titrated for 30 min to an end-tidal concentration of 1.2% (baseline). Rocuronium was infused to 50% (partial) and 95% (profound) depression of the first twitch in a train-of-four response, the order being randomly chosen. Noxious tetanic electrical stimulation was applied at four occasions: 1) at baseline (control measurement), 2 and 3) at each degree of NMB, and 4) after neostigmine reversal. BIS, AAI, and EMG were obtained 2 min before and 2 min after each noxious stimulation. RESULTS: Median BIS and AAI at baseline were 44 (39-50) and 15 (14-16), respectively. The two degrees of NMB did not affect BIS, AAI, and EMG before noxious stimulation. In contrast, profound NMB altered the BIS and AAI responses to noxious stimulation when compared with partial NMB, (BIS P = 0.01, AAI P < 0.01), after neostigmine reversal (BIS P < 0.01, AAI P = 0.01) and compared with baseline (BIS P = 0.08, AAI P = 0.02). No significant increase in EMG was found. CONCLUSION: BIS and AAI responses to noxious tetanic electrical stimulation are affected by the degree of NMB during sevoflurane anesthesia whereas NMB does not affect BIS or AAI in the absence of noxious stimulation.

Object memory in young and aged mice after sevoflurane anaesthesia.

Learning and memory are cognitive functions commonly impaired after surgery, especially in elderly patients. Our aim was to evaluate the effect of sevoflurane anaesthesia on episodic-like memory in young and aged wild-type mice and mice with altered nicotinic cholinergic neurotransmission (beta2KO). Mice learned objects before randomization to control, anaesthesia or sham groups. Anaesthesia was maintained at 2.6% sevoflurane for 2 h, starting immediately after training. Object memory testing was performed after 24 h, when one familiar object was replaced by a nonfamiliar object. While nonanaesthetized mice showed memory retention of the familiar object, anaesthetized wild-type and beta2KO mice showed impaired memory. Sevoflurane anaesthesia thus causes memory impairment in mice regardless of beta2 receptor-mediated nicotinic cholinergic neurotransmission.