Perioperative Continuous Positive Airway Pressure Therapy: A Review With the Emphasis on Randomized Controlled Trials and Obstructive Sleep Apnea.

The perioperative use of continuous positive airway pressure (CPAP) therapy has increased substantially in recent years, particularly in relationship to the treatment of patients with known or suspected obstructive sleep apnea (OSA). OSA is common in the surgical population and is reported as an independent risk factor for postoperative complications, intensive care unit admission, and increased length of hospital stay. A large proportion of OSA patients are undiagnosed at the time of surgery and can therefore not be optimized preoperatively. Nowadays, golden standard treatment of moderate to severe OSA is nightly CPAP at home, often with an autotitration mode. Unfortunately, there are only a handful of randomized clinical trials investigating the effect of preoperative and/or postoperative CPAP treatment in OSA patients, so the perioperative guidelines are based on a combination of randomized clinical trials, observational studies, case studies, and expert opinions. In this review, we have summarized the current evidence regarding the use of perioperative CPAP therapy with an emphasis on patients with OSA. We identified 21 randomized, controlled trials that investigated the effect of CPAP on postoperative physiology and complications in surgical patients. Our review reveals evidence, suggesting that CPAP after surgery improves oxygenation and reduces the need for reintubation and mechanical ventilation after surgery. It is also evident that CPAP reduces apnea and hypopnea frequency and related hypoxemia after surgery. Poor adherence to CPAP in the perioperative setting is a limiting factor in assessing its potential to optimize postoperative cardiorespiratory outcomes. Studies of postoperative outcomes in patients who have previously been prescribed CPAP for OSA and are therefore familiar with its use could help to address this shortcoming, but they are unfortunately lacking. This shortcoming should be addressed in future studies. Furthermore, many of the studies of the postoperative effect of CPAP in OSA patents are small, and therefore, single-center studies and larger randomized, controlled multicenter studies are warranted.

Pre-oxygenation using high-flow nasal oxygen vs. tight facemask during rapid sequence induction.

Pre-oxygenation using high-flow nasal oxygen can decrease the risk of desaturation during rapid sequence induction in patients undergoing emergency surgery. Previous studies were single-centre and often in limited settings. This randomised, international, multicentre trial compared high-flow nasal oxygen with standard facemask pre-oxygenation for rapid sequence induction in emergency surgery at all hours of the day and night. A total of 350 adult patients from six centres in Sweden and one in Switzerland undergoing emergency surgery where rapid sequence induction was required were included and randomly allocated to pre-oxygenation with 100% oxygen using high-flow nasal oxygen or a standard tight-fitting facemask. The primary outcome was the number of patients developing oxygen saturations <93% from the start of pre-oxygenation until 1 min after tracheal intubation. Data from 349 of 350 patients who entered the study were analysed (174 in the high-flow nasal oxygen group and 175 in the facemask group). No difference was detected in the number of patients desaturating <93%, five (2.9%) vs. six (3.4%) patients in the high-flow nasal oxygen and facemask group, respectively (p = 0.77). The risk of desaturation was not increased during on-call hours. No difference was seen in end-tidal carbon dioxide levels in the first breath after tracheal intubation or in the number of patients with signs of regurgitation between groups. These results confirm that high-flow nasal oxygen maintains adequate oxygen levels during pre-oxygenation for rapid sequence induction.

Risks to healthcare workers following tracheal intubation of patients with COVID-19: a prospective international multicentre cohort study.

Healthcare workers involved in aerosol-generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID-19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID-19. Information on tracheal intubation episodes, personal protective equipment use and subsequent provider health status was collected via self-reporting. The primary endpoint was the incidence of laboratory-confirmed COVID-19 diagnosis or new symptoms requiring self-isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure-related factors and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow-up of 32 (18-48 [0-116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1% and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in women, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID-19 subsequently reported a COVID-19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID-19 transmission.

Hypoxic ventilatory response after rocuronium-induced partial neuromuscular blockade in men with obstructive sleep apnoea.

Obstructive sleep apnoea and residual neuromuscular blockade are, independently, known to be risk factors for respiratory complications after major surgery. Residual effects of neuromuscular blocking agents are known to reduce the hypoxic ventilatory response in healthy volunteers. Patients with obstructive sleep apnoea have impaired control of breathing, but it is not known to what extent neuromuscular blocking agents interfere with the regulation of breathing in such patients. In a physiological study in 10 unsedated men with untreated obstructive sleep apnoea, we wished to examine if partial neuromuscular blockade had an effect on hypoxic ventilatory response (isocapnic hypoxia to oxygen saturation of 80%) and hypercapnic ventilatory response (normoxic inspired carbon dioxide 5%). The hypoxic ventilatory response was reduced by 32% (p = 0.016) during residual neuromuscular block (rocuronium to train-of-four ratio 0.7), but the hypercapnic ventilatory response was unaffected. We conclude that neuromuscular blockade specifically depresses peripheral chemosensitivity, and not respiratory muscle function since the hypercapnic ventilatory response was unaffected.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) vs. facemask breathing pre-oxygenation for rapid sequence induction in adults: a prospective randomised non-blinded clinical trial.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) can prolong apnoea time in adults. Therefore, THRIVE used for pre-oxygenation in rapid sequence induction of anaesthesia could extend safe apnoea time during prolonged laryngoscopy and intubation. In this randomised controlled trial, we compared the lowest peripheral oxygen saturation (SpO2 ) during intubation when pre-oxygenating with either traditional facemask or THRIVE. Eighty adult patients, undergoing rapid sequence induction of anaesthesia for emergency surgery, were randomly allocated to pre-oxygenation with 100% oxygen with facemask or with THRIVE. Median (IQR [range]) lowest SpO2 until 1 min after intubation was 99% (97-100 [70-100]%) for the facemask group vs. 99% (99-100 [96-100]%) for the THRIVE group (p = 0.097). Five patients (12.5%) desaturated below 93% when pre-oxygenated with the facemask vs. none in the THRIVE group (p = 0.019). There were no differences in intubation time or apnoea time between the groups. Median intubation time was 51 (34-66 [22-261]) s in the facemask group vs. 48 (38-63 [10-146]) s in the THRIVE group (p = 0.99). Median apnoea time was 109 (86-142 [37-291]) s and 116 (92-146 [63-249]) s when using facemask and THRIVE, respectively (p = 0.49). No signs of regurgitation of gastric content were detected. The data on desaturation indicate potential benefits of oxygenation with THRIVE for rapid sequence induction compared with facemask pre-oxygenation.

Apnoeic oxygenation in adults under general anaesthesia using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) - a physiological study.

BACKGROUND.: Apnoeic oxygenation during anaesthesia has traditionally been limited by the rapid increase in carbon dioxide and subsequent decrease in pH. Using a Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) technique a slower increase in carbon dioxide than earlier studies was seen. Notably, apnoeic oxygenation using THRIVE has not been systematically evaluated with arterial blood gases or in patients undergoing laryngeal surgery. The primary aim of this study was to characterize changes in arterial P O 2 , P CO 2 and pH during apnoeic oxygenation using THRIVE under general anaesthesia. METHODS.: Adult patients, (ASA I-II), undergoing shorter laryngeal surgery under general anaesthesia, were oxygenated during apnoea using THRIVE, 100% oxygen, 40-70 litres min - 1 . A cohort was randomized to hyperventilate during pre-oxygenation. Vital parameters and blood gases were monitored. RESULTS.: Thirty-one patients, age 51 (34-76) yr, BMI 25 (4) were included. Mean apnoea time was 22.5 (4.5) min. Patients were well oxygenated, S pO 2 was never below 91%. The increase in P aCO 2 and end-tidal CO 2 during apnoea was 0.24 (0.05) and 0.12 (0.04) kPa min -1 , respectively. Hyperventilation during pre-oxygenation generated no difference in P aCO 2 at the end of apnoea compared with normoventilation. CONCLUSIONS.: This physiological study of apnoeic oxygenation using THRIVE during laryngeal surgery shows that this technique is able to keep patients with mild systemic disease and a BMI <30 well oxygenated for a period of up to 30 min. The THRIVE concept makes it possible to extend the apnoeic window but monitoring of CO 2 and/or pH is recommended. CLINICAL TRIAL REGISTRATION.: NCT02706431.

Prolonged attenuation of acetylcholine-induced phosphorylation of extracellular signal-regulated kinase 1/2 following sevoflurane exposure.

BACKGROUND: Volatile anaesthetics are known to affect cholinergic receptors. Perturbation of cholinergic signalling can cause cognitive deficits. In this study, we wanted to evaluate acetylcholine-induced intracellular signalling following sevoflurane exposure. METHODS: Pheochromocytoma12 PC12 cells were exposed to 4.6% sevoflurane for 2 h. Subsequently, Western blotting was used to measure acetylcholine-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK) 1/2 and basal Protein kinase B (AKT) phosphorylation. RESULTS: After exposure, acetylcholine-induced ERK 1/2 phosphorylation was reduced to 58 ± 8% [95% confidence interval (CI): 38-77%, P = 0.003] compared with non-exposed controls. At 30 min after the end of sevoflurane administration [at 0.7% sevoflurane (0.102 mM)], ERK 1/2 phosphorylation remained reduced to 57 ± 7% (95% CI: 39-74%, P = 0.001) and was at 120 min [0.02% (0.003 mM] still reduced to 63 ± 10% (95% CI: 37-88%, P = 0.01), compared with control. At 360 min after exposure, acetylcholine-induced ERK 1/2 phosphorylation had recovered to 98 ± 16% (95% CI: 45-152%, P = 0.98) compared with control. In contrast, immediately after sevoflurane exposure, basal AKT phosphorylation was increased by 228 ± 37% (95% CI: 133-324%, P = 0.02) but had returned to control levels at 30 min after exposure, 172 ± 67% (95% CI: 0-356%, P = 0.34). CONCLUSION: Sevoflurane exposure has differential effects on different intracellular signalling pathways. On one hand, we observed a prolonged attenuation of acetylcholine-induced ERK 1/2 phosphorylation that persisted even when sevoflurane concentrations close to detection level. On the other hand, basal AKT phosphorylation was increased twofold during sevoflurane exposure, with a rapid return to baseline levels after exposure. We speculate that the effects on acetylcholine-induced intracellular signalling observed in our in vitro model could be of relevance also for cholinergic signalling in vivo following sevoflurane exposure.

Reduced effect of propofol at human {alpha}1{beta}2(N289M){gamma}2 and {alpha}2{beta}3(N290M){gamma}2 mutant GABA(A) receptors.

BACKGROUND: Propofol is an i.v. anaesthetic commonly used during general anaesthesia and intensive care. It is known that the second transmembrane segment of the beta subunit in the GABA(A) receptor is an important target for the effects of propofol; however, this has not been investigated in human receptors. The aim of this study was to investigate the effect of propofol on human beta2 and beta3 GABA(A) subunits with point mutations corresponding to the N265M mutation in the rat beta2 and beta3 subunits. METHODS: Asparagine-to-methionine replacement at amino acid position 289 and 290 (N289M and N290M) in the beta2 and beta3 GABA(A) receptor subunits, respectively, was accomplished by site-directed mutagenesis. Thereafter, subunits for three human wild-type (alpha1beta2gamma2, alpha2beta2gamma2, and alpha2beta3gamma2) and two mutant GABA(A) receptor channels [alpha1beta2(N289M)gamma2 and alpha2beta3(N290M)gamma2] were introduced into Xenopus oocytes and studied with two-electrode voltage clamp. RESULTS: The mutant receptors left-shifted the GABA concentration-response curve. In comparison with the wild-type receptors, both the positive modulatory and the agonistic effects of propofol were strongly reduced in potency and amplitude at both mutated GABA(A) channels. CONCLUSIONS: We demonstrate that N289M or N290M mutation in human GABA(A) beta2 and beta3 subunits increases sensitivity to GABA, which is in contrast to the corresponding rat N265M mutation. Furthermore, the N289M and N289M mutations reduce both the potentiation of GABA-induced currents and the direct effect of propofol on channels incorporating either of the mutated subunits, which confirms earlier findings concerning the corresponding mutation in rat receptors and knock-in mice.