Pre-oxygenation using high-flow nasal oxygen versus tight facemask in trauma patients undergoing emergency anaesthesia.

BACKGROUND: Patients suffering from major traumatic injuries frequently require emergency anaesthesia. Due to often compromised physiology and the time-sensitive management, trauma patients may be more prone to desaturate during induction of anaesthesia. We hypothesised that pre-oxygenation using high-flow nasal oxygen would decrease the risk of desaturation during induction of anaesthesia in trauma patients and the study therefore aimed to compare the frequency of desaturation when pre-oxygenation was performed with high-flow nasal oxygen or a traditional facemask. METHODS: This exploratory, prospective, before-and-after study was conducted at the Karolinska University Hospital, Sweden. Adult (≥18 years of age) patients suffering major traumatic injuries needing emergency anaesthesia were included around the clock. Patients were pre-oxygenated using a tight-fitting facemask during the first nine months of enrollment. High-flow nasal oxygen was then introduced as a method for pre-oxygenation of trauma patients. The primary outcome was the proportion of patients desaturating <93% during induction of anaesthesia, assessed from the start of pre-oxygenation until one minute after intubation. Secondary outcomes included perceived difficulty of pre-oxygenation among anaesthetists (assessed on a scale between 1 and 10) and safety outcomes, such as incidence of regurgitations and intracranial gas (assessed radiologically). RESULTS: Data from 96 patients were analysed. Facemask pre-oxygenation was performed in 66 patients, while 30 patients were pre-oxygenated with high-flow nasal oxygen. The most frequent trauma mechanisms were stabbing injuries (n = 34 (35%)) and fall injuries (n = 21 (22%)). There were no differences in patient characteristics between the groups. Eight (12%) versus three (10%) patients desaturated <93% in the facemask and high-flow nasal oxygen group respectively, OR 0.81 (95% CI 0.20-3.28), p = .76. Anaesthetists assessed pre-oxygenation using high-flow nasal oxygen as easier compared to facemask pre-oxygenation. No patient in any group showed signs of regurgitation. Among patients with facial or skull fractures requiring anaesthesia before radiology was performed, intracranial gas was seen in four (40%) patients pre-oxygenated with a facemask and in no patient pre-oxygenated with HFNO (p = .23). CONCLUSION: In this prospective study investigating trauma patients undergoing emergency anaesthesia, we could not see any difference in the number of patients desaturating when pre-oxygenation was performed with high-flow nasal oxygen compared to a tight-fitting facemask. Pre-oxygenation using high-flow nasal oxygen was assessed as easier compared to facemask pre-oxygenation.

In-situ simulation of CPR in the emergency department - A tool for continuous improvement of the initial resuscitation.

Background: Simulating CPR scenarios in a clinical environment has been described as a method for mitigating latent safety threats. Therefore, we implemented regular inter-professional, multidisciplinary in-situ simulations in the emergency department (ED). Aim: To iterate a line-up and action cards for initial CPR management. To examine the experiences among participants regarding attitudes towards simulation and if they perceived any benefits for their patients after the participation. Method: In 2021 we performed 7 in-situ simulations (15-minute simulation, 15-minute hot debrief) in the ED with the CPR team including doctors and nurses from the ED and anaesthesiology department. A questionnaire was sent to the 48 participants the same day and after 3 and 18 months. Answers were given as yes/no or on a Likert scale 0-5 and are presented as median values with interquartile range (IQR) or frequencies. Results: A line-up and 9 action cards were created. The response rate of the three questionnaires were 52, 23, and 43%, respectively. In total, 100% would recommend the in-situ simulation to a co-worker. Participants perceived that real patients (5 [3-5]) as well as themselves, (5 [3.5-5]), had benefited from the simulation up to 18 months after. Conclusion: Thirty-minute in-situ simulations are feasible to implement in the ED and simulation observations were useful for development of standardised role descriptions for resuscitation in the ED. Participants self-report benefit for themselves as well as their patients.

Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision.

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59-74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51, 789-808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.

Pre-oxygenation using high-flow nasal oxygen in parturients undergoing caesarean section in general anaesthesia: A prospective, multi-centre, pilot study.

BACKGROUND: Parturients undergoing caesarean section in general anaesthesia have an increased risk of desaturating during anaesthesia induction. Pre- and peri-oxygenation with high-flow nasal oxygen prolong the safe apnoea time but data on parturients undergoing caesarean section under general anaesthesia are limited. This pilot study aimed to investigate the clinical effects and frequency of desaturation in parturients undergoing caesarean section in general anaesthesia pre- and peri-oxygenated with high-flow nasal oxygen and compare this to traditional pre-oxygenation using a facemask. METHODS: In this prospective, non-randomised, multi-centre study we included pregnant women with a gestational age ≥30 weeks undergoing caesarean section under general anaesthesia. All parturients were asked to participate in the intervention group consisting of pre-oxygenation using high-flow nasal oxygen. Parturients declining participation were pre-oxygenated with a traditional facemask. Primary outcome was the proportion of parturients desaturating below 93% from start of pre-oxygenation until 1 min after tracheal intubation. Secondary outcomes investigated end-tidal oxygen concentrations after tracheal intubation and the proportion of parturients with signs of regurgitation. RESULTS: A total of 34 parturients were included, 25 pre- and peri-oxygenated with high-flow nasal oxygen and 9 pre-oxygenated with facemask. No difference in patient or airway characteristics could be seen except for a higher BMI in the high-flow nasal oxygen group (31.4 kg m-2 [4.7] vs. 27.7 kg m-2 [3.1]; p = .034). No woman in any of the two groups desaturated below 93%. The lowest peripheral oxygen saturation observed, in any parturient, was 97%. There was no difference detected in end-tidal oxygen concentration after tracheal intubation, 87% (6) in the high-flow nasal oxygen group vs 80% (15) in the facemask group (p = .308). No signs of regurgitation, in any parturient, were seen. CONCLUSION: Pre- and peri-oxygenation with high-flow nasal oxygen maintain adequate oxygen saturation levels during induction of anaesthesia also in parturients. Regurgitation of gastric content did not occur in any parturient and no other safety concerns were observed in this pilot study.

Cardiopulmonary haemodynamic effects and gas exchange during apnoeic oxygenation with high-flow and low-flow nasal oxygen: A large animal study.

BACKGROUND: Apnoeic oxygenation with high-flow nasal oxygen prolongs the safe apnoeic period during induction of general anaesthesia. However, central haemodynamic effects and the characteristics of central gaseous exchange remain unexplored. OBJECTIVE: To describe mean pulmonary arterial pressure along with arterial and mixed venous blood gases and central haemodynamic parameters during apnoeic oxygenation with low-flow and high-flow nasal oxygen in pigs. DESIGN: Experimental crossover study. SETTING: Animal study of 10 healthy Swedish landrace pigs at Karolinska Institutet, Sweden, April-May 2021. INTERVENTION: The pigs were anaesthetised, their tracheas intubated and their pulmonary arteries catheterised. The animals were preoxygenated and paralysed before apnoea. Apnoeic periods between 45 and 60 min were implemented with either 70 or 10 l min -1 100% O 2 delivered via nasal catheters. In addition, seven animals underwent an apnoea without fresh gas flow. Cardiopulmonary parameters and blood gases were measured repeatedly. MAIN OUTCOME MEASURES: Mean pulmonary arterial pressure during apnoeic oxygenation with high-flow and low-flow oxygen. RESULTS: Nine pigs completed two apnoeic periods of at least 45 min with a Pa O 2 not lower than 13 kPa. The mean pulmonary arterial pressure increased during 45 min of apnoea, from 18 ±â€Š1 to 33 ±â€Š2 mmHg and 18 ±â€Š1 to 35 ±â€Š2 mmHg, at 70 and 10 l min -1 O 2 , respectively ( P  < 0.001); there was no difference between the groups ( P  = 0.87). The Pa CO 2 increased by 0.48 ±â€Š0.07 and 0.52 ±â€Š0.04 kPa min -1 , at 70 and 10 l min -1 O 2 , respectively; there was no difference between the groups ( P  = 0.22). During apnoea without fresh gas flow, the SpO 2 declined to less than 85% after 155 ±â€Š11 s. CONCLUSION: During apnoeic oxygenation in pigs, the mean pulmonary arterial pressure increased two-fold and Pa CO 2 five-fold after 45 min, while the arterial oxygen levels were maintained over 13 kPa, irrespective of high-flow or low-flow oxygen.

The Use of Levosimendan after Out-of-Hospital Cardiac Arrest and Its Association with Outcome-An Observational Study.

Background: Levosimendan improves resuscitation rates and cardiac performance in animal cardiac arrest models. The aim of this study was to describe the use of levosimendan in out-of-hospital cardiac arrest (OHCA) patients and its association with outcome. Methods: A retrospective observational study of OHCA patients admitted to six intensive care units in Stockholm, Sweden, between 2010 and 2016. Patients treated with levosimendan within 24 h from admission were compared with those not treated with levosimendan. Propensity score matching and multivariable logistic regression analysis were used to assess the association between levosimendan treatment and 30-day mortality Results: Levosimendan treatment was initiated in 94/940 (10%) patients within 24 h. The proportion of men (81%, vs. 67%, p = 0.007), initial shockable rhythm (66% vs. 37%, p < 0.001), acute myocardial infarction, AMI (47% vs. 24%, p < 0.001) and need for vasoactive support (98% vs. 61%, p < 0.001) were higher among patients treated with levosimendan. After adjustment for age, sex, bystander cardiopulmonary resuscitation, witnessed status, initial rhythm and AMI, the odds ratio (OR) for 30-day mortality in the levosimendan group compared to the no-levosimendan group was 0.94 (95% Confidence interval [CI], 0.56−1.57, p = 0.82). Similar results were seen when using a propensity score analysis comparing patients with circulatory shock. Conclusions: In this observational study of OHCA patients, levosimendan was used in a limited patient group, most often in those with initial shockable rhythms, acute myocardial infarction and with a high need for vasopressors. In this limited patient cohort, levosimendan treatment was not associated with 30-day mortality. However, a better matching of patient factors and indications for use is required to derive conclusions on associations with outcome.

Upper Airway Collapsibility during Dexmedetomidine and Propofol Sedation in Healthy Volunteers: A Nonblinded Randomized Crossover Study.

BACKGROUND: Dexmedetomidine is a sedative promoted as having minimal impact on ventilatory drive or upper airway muscle activity. However, a trial recently demonstrated impaired ventilatory drive and induction of apneas in sedated volunteers. The present study measured upper airway collapsibility during dexmedetomidine sedation and related it to propofol. METHODS: Twelve volunteers (seven female) entered this nonblinded, randomized crossover study. Upper airway collapsibility (pharyngeal critical pressure) was measured during low and moderate infusion rates of propofol or dexmedetomidine. A bolus dose was followed by low (0.5 µg · kg · h or 42 µg · kg · min) and moderate (1.5 µg · kg · h or 83 µg · kg · min) rates of infusion of dexmedetomidine and propofol, respectively. RESULTS: Complete data sets were obtained from nine volunteers (median age [range], 46 [23 to 66] yr; body mass index, 25.4 [20.3 to 32.4] kg/m). The Bispectral Index score at time of pharyngeal critical pressure measurements was 74 ± 10 and 65 ± 13 (mean difference, 9; 95% CI, 3 to 16; P = 0.011) during low infusion rates versus 57 ± 16 and 39 ± 12 (mean difference, 18; 95% CI, 8 to 28; P = 0.003) during moderate infusion rates of dexmedetomidine and propofol, respectively. A difference in pharyngeal critical pressure during sedation with dexmedetomidine or propofol could not be shown at either the low or moderate infusion rate. Median (interquartile range) pharyngeal critical pressure was -2.0 (less than -15 to 2.3) and 0.9 (less than -15 to 1.5) cm H2O (mean difference, 0.9; 95% CI, -4.7 to 3.1) during low infusion rates (P = 0. 595) versus 0.3 (-9.2 to 1.4) and -0.6 (-7.7 to 1.3) cm H2O (mean difference, 0.0; 95% CI, -2.1 to 2.1; P = 0.980) during moderate infusion of dexmedetomidine and propofol, respectively. A strong linear relationship between pharyngeal critical pressure during dexmedetomidine and propofol sedation was evident at low (r = 0.82; P = 0.007) and moderate (r = 0.90; P < 0.001) infusion rates. CONCLUSIONS: These observations suggest that dexmedetomidine sedation does not inherently protect against upper airway obstruction.

Hypoxia Regulates MicroRNA Expression in the Human Carotid Body.

How hypoxia regulates gene expression in the human carotid body (CB) remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the impact of important post-transcriptional regulators, such as non-coding RNAs, and in particular miRNAs is not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins.

Hypoxia regulates microRNA expression in the human carotid body.

The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins.

The Human Carotid Body Gene Expression and Function in Signaling of Hypoxia and Inflammation.

Although animal carotid body oxygen sensing and signaling has been extensively investigated, the human carotid body remains essentially uncharacterized. Therefore, we aimed to study the human carotid body in terms of morphology, global and specific expression of sensing and signaling genes as well as inflammatory genes. The human carotid body response to brief or prolonged hypoxia was studied in carotid body slices from adult surgical patients and ACh, ATP and cytokine release was analyzed. We demonstrate that the human carotid body expresses key oxygen sensing and signaling genes in similarity with animal carotid bodies with a few diverging data. The human carotid body moreover shows enrichment of genes in the inflammatory response and releases pro and anti-inflammatory cytokines in response to prolonged hypoxia. In response to acute hypoxia the human carotid body releases ACh and ATP and we thus translate previous findings in animal models to human tissue. We conclude that by releasing pro- and anti-inflammatory cytokines during hypoxia the human carotid body displays a structural and functional capacity to participate in sensing and mediating systemic inflammation.

The human carotid body releases acetylcholine, ATP and cytokines during hypoxia.

Studies on experimental animals established that the carotid bodies are sensory organs for detecting arterial blood O2 levels and that the ensuing chemosensory reflex is a major regulator of cardiorespiratory functions during hypoxia. However, little information is available on the human carotid body responses to hypoxia. The present study was performed on human carotid bodies obtained from surgical patients undergoing elective head and neck cancer surgery. Our results show that exposing carotid body slices to hypoxia for a period as brief as 5 min markedly facilitates the release of ACh and ATP. Furthermore, prolonged hypoxia for 1 h induces an increased release of interleukin (IL)-1ß, IL-4, IL-6, IL-8 and IL-10. Immunohistochemical analysis revealed that type 1 cells of the human carotid body express an array of cytokine receptors as well as hypoxia-inducible factor-1α and hypoxia-inducible factor-2α. Taken together, these results demonstrate that ACh and ATP are released from the human carotid body in response to hypoxia, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. The finding that the human carotid body releases cytokines in response to hypoxia adds to the growing body of information suggesting that the carotid body may play a role in detecting inflammation, providing a link between the immune system and the nervous system.

The human carotid body transcriptome with focus on oxygen sensing and inflammation--a comparative analysis.

The carotid body (CB) is the key oxygen sensing organ. While the expression of CB specific genes is relatively well studied in animals, corresponding data for the human CB are missing. In this study we used five surgically removed human CBs to characterize the CB transcriptome with microarray and PCR analyses, and compared the results with mice data. In silico approaches demonstrated a unique gene expression profile of the human and mouse CB transcriptomes and an unexpected upregulation of both human and mouse CB genes involved in the inflammatory response compared to brain and adrenal gland data. Human CBs express most of the genes previously proposed to be involved in oxygen sensing and signalling based on animal studies, including NOX2, AMPK, CSE and oxygen sensitive K+ channels. In the TASK subfamily of K+ channels, TASK-1 is expressed in human CBs, while TASK-3 and TASK-5 are absent, although we demonstrated both TASK-1 and TASK-3 in one of the mouse reference strains. Maxi-K was expressed exclusively as the spliced variant ZERO in the human CB. In summary, the human CB transcriptome shares important features with the mouse CB, but also differs significantly in the expression of a number of CB chemosensory genes. This study provides key information for future functional investigations on the human carotid body.

The human carotid body: expression of oxygen sensing and signaling genes of relevance for anesthesia.

BACKGROUND: Hypoxia is a common cause of adverse events in the postoperative period, where respiratory depression due to residual effects of drugs used in anesthesia is an important underlying factor. General anesthetics and neuromuscular blocking agents reduce the human ventilatory response to hypoxia. Although the carotid body (CB) is the major oxygen sensor in humans, critical oxygen sensing and signaling pathways have been investigated only in animals so far. Thus, the aim of this study was to characterize the expression of key genes and localization of their products involved in the human oxygen sensing and signaling pathways with a focus on receptor systems and ion channels of relevance in anesthesia. METHODS: Six CBs were removed unilaterally from patients undergoing radical neck dissection. The gene expression and cell-specific protein localization in the CBs were investigated with DNA microarrays, real-time polymerase chain reaction, and immunohistochemistry. RESULTS: We found gene expression of the oxygen-sensing pathway, heme oxygenase 2, and the K channels TASK (TWIK-related acid sensitive K channel)-1 and BK (large-conductance potassium channel). In addition, we show the expression of critical receptor subunits such as γ-aminobutyric acid A (α2, ß3, and γ2), nicotinic acetylcholine receptors (α3, α7, and ß2), purinoceptors (A2A and P2X2), and the dopamine D2 receptor. CONCLUSIONS: In unique samples of the human CB, we here demonstrate presence of critical proteins in the oxygen-sensing and signaling cascade. Our findings demonstrate similarities to, but also important differences from, established animal models. In addition, our work establishes an essential platform for studying the interaction between anesthetic drugs and human CB chemoreception.

Presence of nicotinic, purinergic and dopaminergic receptors and the TASK-1 K+-channel in the mouse carotid body.

We have characterized the mouse carotid body (CB) with special attention to nicotinic, purinergic and dopaminergic receptors as well as the TASK-1 K(+)-channel. Mouse CB sections were stained immunohistochemically and visualized using fluorescent and confocal microscopy. The CB type 1 cells contained the alpha3 (n=8), alpha4 (n=7), alpha7 (n=4) and beta2 (n=3) nicotinic acetylcholine receptor (nAChR) subunits, the ATP-receptors P2X(2) (n=15) and P2X(3) (n=9), the dopamine D(2) receptor (n=9) and the TASK-1 K(+)-channel (n=7). Here we report the presence of alpha3, alpha4, alpha7 and beta2 nAChR subunits, the D(2) receptor and the TASK-1 K(+)-channel in the mouse CB. Also, we confirm the presence of the P2X(2) and P2X(3) receptors in mouse CB. Thus, we have localized nicotinergic, purinergic and dopaminergic receptors and the TASK-1 K(+)-channel on a protein level in one species. Our data are in line with the theory that the CB chemoreceptor cell hosts an orchestra of receptor systems that ultimately modulate the response to hypoxia.

Pronounced depression by propofol on carotid body response to CO2 and K+-induced carotid body activation.

Propofol is a commonly used anesthetic agent, and it attenuates hypoxic ventilatory response in humans. Propofol reduce in vivo and in vitro carotid body responses to hypoxia as well as to nicotine in experimental animals. In the present study we examined the effects of propofol on carotid body responses to hypercapnia and K(+)-induced carotid body activation and compared these effects with hypoxia in an in vitro rabbit carotid body preparation. Hypoxia, hypercapnia and potassium increased the carotid sinus nerve activity and propofol attenuated the chemoreceptor responses to all three stimuli. However, the magnitude of propofol-induced attenuation was greater for hypercapnic and K(+)-induced carotid body activation compared to the hypoxic response. These observations suggest that propofol-induced attenuation of the hypoxic response is partly secondary to depression of chemoreceptor response to hypercapnia inhibiting the synergistic interactions between O(2) and CO(2) and may involve CO(2)/H(+) sensitive K(+) channels.