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.

Current concepts in neuromuscular transmission.

The neuromuscular junction (NMJ) is structured and powered to transduce electrical activity from the distal nerve terminal of a motor neurone via the neuromuscular cleft to the post-junctional muscle membrane to ultimately generate muscle contraction. Our understanding of this complex function has expanded over many years, and the NMJ has served as a prototype for how different synapses operate in the peripheral and central nervous systems. The NMJ has a presynaptic part which is synonymous with the distal nerve ending, being responsible for neurotransmitter synthesis, packaging into vesicles, and subsequent vesicle transportation to active release sites where vesicle docking, fusion, and release of acetylcholine and other co-released transmitters finally take place. The synaptic cleft, filled with large molecular complexes that guarantee ultrastructural NMJ arrangement and signal transduction, allows for rapid diffusion and degradation of the neurotransmitter. The postsynaptic part consists of a folded muscle membrane into which nicotinic acetylcholine receptors (nAChRs) directly opposite the presynaptic active release sites are mounted and fixed by a cytoskeleton. This specialized postsynaptic region is closely associated with the perijunctional zone where a high density of sodium channels promote and amplify the signal in order to guarantee the propagation of the electrical activity to generate muscle contraction. The transduction process is maintained at load (i.e. high stimulus frequency) by a presynaptic mechanism allowing for sustained transmitter release over time at high demand. This positive feedback mechanism relies on neuronal nAChRs present on the distal nerve terminal, whereas the continuation of the transduction process at the postsynaptic part relies on the classical muscle type nAChR. In this review, we will focus on recent findings of potential clinical importance that will advance our understanding of the effects of neuromuscular blocking agents and neuromuscular monitoring and also our management of disorders of the neuromuscular system within anaesthesia and intensive care.

Basic principles of neuromuscular transmission.

Neuromuscular transmission at the skeletal muscle occurs when a quantum of acetylcholine from the nerve ending is released and binds to the nicotinic acetylcholine receptors on the postjunctional muscle membrane. The nicotinic acetylcholine receptors on the endplate respond by opening channels for the influx of sodium ions and subsequent endplate depolarisation leads to muscle contraction. The acetylcholine immediately detaches from the receptor and is hydrolysed by acetylcholinesterase enzyme. Suxamethonium is a cholinergic agonist stimulating the muscle nicotinic acetylcholine receptors prior to causing neuromuscular block. Non-depolarising neuromuscular blocking drugs bind to the nicotinic acetylcholine receptors preventing the binding of acetylcholine. Non-depolarising neuromuscular blocking drugs also inhibit prejunctional alpha3beta2 nicotinic acetylcholine autoreceptors, which can be seen in the clinical setting as train-of-four fade. In some pathological states such as denervation, burns, immobilisation, inflammation and sepsis, there is expression of other subtypes of nicotinic acetylcholine receptors with upregulation of these receptors throughout the muscle membrane. The responses of these receptors to suxamethonium and non-depolarising neuromuscular blocking drugs are different and explain some of the aberrant responses to neuromuscular blocking drugs.

Digital nerve somatosensory evoked potentials and MRI. Correlation analysis in patients with symptomatic cervical spine disorders.

OBJECTIVES: Analysis of the relationship between the symptoms, digital nerve somatosensory evoked potentials (D-SEP) and MRI, in patients with symptomatic cervical spine disorders (CSD). MATERIALS AND METHODS: MRI and D-SEP following electrical stimulation of digits I, III and V in 44 patients. RESULTS: Symptoms in the fingers correlated significantly with disk herniation at the corresponding cervical level and with spinal cord impingement at one or two adjacent rostral segments on MRI. D-SEP was abnormal in 52% of all patients. Among them, the groups with multiple and single level involved on MRI had 62% and 30% of abnormal somatosensory evoked potentials (SEP), respectively. Digit I-SEP abnormality was more often localized at the root level, while digit V-SEP at the spinal cord level above the dorsal nucleus. D-SEP correlated best with compression of the spinal cord at adjacent upper and especially the most rostral (C3-5) levels on MRI. CONCLUSIONS: Accurate correlation of D-SEP and symptoms with MRI is essential for correct localization of lesions in patients with CSD.

Cerebrospinal fluid hydrodynamics after placement of a shunt with an antisiphon device: a long-term study.

OBJECT: Few studies have been performed to investigate the cerebrospinal fluid (CSF) hydrodynamic profile in patients with idiopathic adult hydrocephalus syndrome (IAHS) before and after shunt implantation. The authors compared the in vivo CSF hydrodynamic properties, including the degree of gravity-induced CSF flow, of a shunt with an antisiphon device with a standard shunt. METHODS: Twelve patients with IAHS underwent insertion of shunts with Delta valves. Clinical testing, magnetic resonance imaging, and CSF hydrodynamic investigations were conducted with intracranial pressure (ICP), gravity effect, and pressure-flow curve of the shunt estimated at baseline and at 3 and 12 months postoperatively. No shunt was revised. Despite postoperative clinical improvement in all patients who received Delta valves, the mean ICP was only moderately reduced (mean decrease at 3 months 0.3 kPa [p = 0.02], at 12 months 0.2 kPa [not significant]). Patients with the greatest increase in ICP preoperatively had the most pronounced decrease postoperatively. The hydrostatic effect of the Delta valves was significantly lower than with the Hakim shunts (0.1-0.2 kPa compared with 0.6 kPa). The increased conductance (that is, lowered resistance) was up to 14 times higher with the Delta valves compared with preoperative levels. CONCLUSIONS: The function of a CSF shunt may be more complicated than previously thought; the subcutaneous pressure acting on the antisiphon device can modify the shunt characteristics. A compensatory increase in CSF production may counteract the increased outflow through the shunt. The improved CSF outflow conductance may increase the intracranial compliance and thereby dampen a pathological ICP waveform.

Three-year survival and functional outcome of patients with idiopathic adult hydrocephalus syndrome.

The functional outcome of 42 patients with idiopathic adult hydrocephalus syndrome (IAHS) was followed over a 3-year period after shunting. Survival curves were compared with those of age-matched healthy elderly subjects and patients with first-ever ischemic stroke. Twenty-seven patients with IAHS were improved 3 months after the operation and 11 remained improved at the 3-year follow-up. The case fatality in patients with stroke and those with IAHS was similar (32% versus 28%), but the relative risk of death among IAHS patients compared to a general elderly population was 3.3.

Lateral sinus thrombosis after untreated otitis media. A clinical problem--again?

Antimicrobial agents have greatly reduced the incidence of intracranial complications of infections of the middle ear and mastoid. Too many prescriptions and overconsumption of antibiotics when otitis media is suspected has caused resistance to many antibiotics, leading to a pronounced and justifiable desire to reduce the widespread excessive use of antibiotics. The possible untoward consequences of a too restricted antibiotic policy, however, is illustrated by the following case of a 14-year-old boy who, after non-treatment of an ear infection, fell ill with one-sided headache and vomiting caused by a lateral sinus thrombosis. After intravenous treatment with antibiotics, anticoagulants and ventilation of the middle ear, the infection was cured without complications. This case calls attention to the symptoms of otitic complications arising outside the temporal bone. The physician must always bear in mind the possibility of an unusual event. The general treatment of endocranial complications is outlined, giving details of the treatment given in this special case. We stress that one should not be too cautious in prescribing antibiotics in otitis media.