Recent experimental observations suggest that, in addition to induce neuroapoptosis, anesthetics can also interfere with synaptogenesis during brain development. The aim of this study was to pursue ...this issue by evaluating the exposure time-dependent effects of volatile anesthetics on neuronal cytoarchitecture in 16-day-old rats, a developmental stage characterized by intense synaptogenesis in the cerebral cortex.
Whistar rats underwent isoflurane (1.5%), sevoflurane (2.5%), or desflurane (7%) anesthesia for 30, 60, and 120 min at postnatal day 16, and the effect of these treatments on neuronal cytoarchitecture was evaluated 6 h after the initiation of anesthesia. Cell death was assessed using Fluoro-Jade B staining and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Ionotophoretic injections into layer 5 pyramidal neurons in the medial prefrontal cortex allowed visualization of dendritic arbor. Tracing of dendritic tree was carried out using the Neurolucida station (Microbrightfield, Williston, VT), whereas dendritic spines were analyzed using confocal microscopy.
Up to a 2-h-long exposure, none of the volatile drugs induced neuronal cell death or significant changes in gross dendritic arbor pattern of layer 5 pyramidal neurons in pups at postnatal day 16. In contrast, these drugs significantly increased dendritic spine density on dendritic shafts of these cells. Importantly, considerable differences were found between these three volatile agents in terms of exposure time-dependent effects on dendritic spine density.
These new results suggest that volatile anesthetics, with different potencies and without inducing cell death, could rapidly interfere with physiologic patterns of synaptogenesis and thus might impair appropriate circuit assembly in the developing cerebral cortex.
Summary Background Perioperative respiratory adverse events in children are one of the major causes of morbidity and mortality during paediatric anaesthesia. We aimed to identify associations between ...family history, anaesthesia management, and occurrence of perioperative respiratory adverse events. Methods We prospectively included all children who had general anaesthesia for surgical or medical interventions, elective or urgent procedures at Princess Margaret Hospital for Children, Perth, Australia, from Feb 1, 2007, to Jan 31, 2008. On the day of surgery, anaesthetists in charge of paediatric patients completed an adapted version of the International Study Group for Asthma and Allergies in Childhood questionnaire. We collected data on family medical history of asthma, atopy, allergy, upper respiratory tract infection, and passive smoking. Anaesthesia management and all perioperative respiratory adverse events were recorded. Findings 9297 questionnaires were available for analysis. A positive respiratory history (nocturnal dry cough, wheezing during exercise, wheezing more than three times in the past 12 months, or a history of present or past eczema) was associated with an increased risk for bronchospasm (relative risk RR 8·46, 95% CI 6·18–11·59; p<0·0001), laryngospasm (4·13, 3·37–5·08; p<0·0001), and perioperative cough, desaturation, or airway obstruction (3·05, 2·76–3·37; p<0·0001). Upper respiratory tract infection was associated with an increased risk for perioperative respiratory adverse events only when symptoms were present (RR 2·05, 95% CI 1·82–2·31; p<0·0001) or less than 2 weeks before the procedure (2·34, 2·07–2·66; p<0·0001), whereas symptoms of upper respiratory tract infection 2–4 weeks before the procedure significantly lowered the incidence of perioperative respiratory adverse events (0·66, 0·53–0·81; p<0·0001). A history of at least two family members having asthma, atopy, or smoking increased the risk for perioperative respiratory adverse events (all p<0·0001). Risk was lower with intravenous induction compared with inhalational induction (all p<0·0001), inhalational compared with intravenous maintenance of anaesthesia (all p<0·0001), airway management by a specialist paediatric anaesthetist compared with a registrar (all p<0·0001), and use of face mask compared with tracheal intubation (all p<0·0001). Interpretation Children at high risk for perioperative respiratory adverse events could be systematically identified at the preanaesthetic assessment and thus can benefit from a specifically targeted anaesthesia management. Funding Department of Anaesthesia, Princess Margaret Hospital for Children, Swiss Foundation for Grants in Biology and Medicine, and the Voluntary Academic Society Basel.
Abstract
Severe COVID-19-related acute respiratory distress syndrome (C-ARDS) requires mechanical ventilation. While this intervention is often performed in the prone position to improve oxygenation, ...the underlying mechanisms responsible for the improvement in respiratory function during invasive ventilation and awake prone positioning in C-ARDS have not yet been elucidated. In this prospective observational trial, we evaluated the respiratory function of C-ARDS patients while in the supine and prone positions during invasive (n = 13) or non-invasive ventilation (n = 15). The primary endpoint was the positional change in lung regional aeration, assessed with electrical impedance tomography. Secondary endpoints included parameters of ventilation and oxygenation, volumetric capnography, respiratory system mechanics and intrapulmonary shunt fraction. In comparison to the supine position, the prone position significantly increased ventilation distribution in dorsal lung zones for patients under invasive ventilation (53.3 ± 18.3% vs. 43.8 ± 12.3%, percentage of dorsal lung aeration ± standard deviation in prone and supine positions, respectively;
p
= 0.014); whereas, regional aeration in both positions did not change during non-invasive ventilation (36.4 ± 11.4% vs. 33.7 ± 10.1%;
p
= 0.43). Prone positioning significantly improved the oxygenation both during invasive and non-invasive ventilation. For invasively ventilated patients reduced intrapulmonary shunt fraction, ventilation dead space and respiratory resistance were observed in the prone position. Oxygenation is improved during non-invasive and invasive ventilation with prone positioning in patients with C-ARDS. Different mechanisms may underly this benefit during these two ventilation modalities, driven by improved distribution of lung regional aeration, intrapulmonary shunt fraction and ventilation-perfusion matching. However, the differences in the severity of C-ARDS may have biased the sensitivity of electrical impedance tomography when comparing positional changes between the protocol groups.
Trial registration: ClinicalTrials.gov (NCT04359407) and Registered 24 April 2020,
https://clinicaltrials.gov/ct2/show/NCT04359407
.
Abstract
Background
Benefits of variable mechanical ventilation based on the physiological breathing pattern have been observed both in healthy and injured lungs. These benefits have not been ...characterized in pediatric models and the effect of this ventilation mode on regional distribution of lung inflammation also remains controversial. Here, we compare structural, molecular and functional outcomes reflecting regional inflammation between PVV and conventional pressure-controlled ventilation (PCV) in a pediatric model of healthy lungs and acute respiratory distress syndrome (ARDS).
Methods
New-Zealand White rabbit pups (n = 36, 670 ± 20 g half-width 95% confidence interval), with healthy lungs or after induction of ARDS, were randomized to five hours of mechanical ventilation with PCV or PVV. Regional lung aeration, inflammation and perfusion were assessed using x-ray computed tomography, positron-emission tomography and single-photon emission computed tomography, respectively. Ventilation parameters, blood gases and respiratory tissue elastance were recorded hourly.
Results
Mechanical ventilation worsened respiratory elastance in healthy and ARDS animals ventilated with PCV (11 ± 8%, 6 ± 3%, p < 0.04), however, this trend was improved by PVV (1 ± 4%, − 6 ± 2%). Animals receiving PVV presented reduced inflammation as assessed by lung normalized
18
Ffluorodeoxyglucose uptake in healthy (1.49 ± 0.62 standardized uptake value, SUV) and ARDS animals (1.86 ± 0.47 SUV) compared to PCV (2.33 ± 0.775 and 2.28 ± 0.3 SUV, respectively, p < 0.05), particularly in the well and poorly aerated lung zones. No benefit of PVV could be detected on regional blood perfusion or blood gas parameters.
Conclusions
Variable ventilation based on a physiological respiratory pattern, compared to conventional pressure-controlled ventilation, reduced global and regional inflammation in both healthy and injured lungs of juvenile rabbits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lung recruitment maneuvers following one-lung ventilation (OLV) increase the risk for the development of acute lung injury. The application of continuous negative extrathoracic pressure (CNEP) is ...gaining interest both in intubated and non-intubated patients. However, there is still a lack of knowledge on the ability of CNEP support to recruit whole lung atelectasis following OLV. We investigated the effects of CNEP following OLV on lung expansion, gas exchange, and hemodynamics. Ten pigs were anesthetized and mechanically ventilated with pressure-regulated volume control mode (PRVC; FiO
: 0.5, Fr: 30-35/min, VT: 7 mL/kg, PEEP: 5 cmH
O) for 1 hour, then baseline (BL) data for gas exchange (arterial partial pressure of oxygen, PaO
; and carbon dioxide, PaCO
), ventilation and hemodynamical parameters and lung aeration by electrical impedance tomography were recorded. Subsequently, an endobronchial blocker was inserted, and OLV was applied with a reduced VT of 5 mL/kg. Following a new set of measurements after 1 h of OLV, two-lung ventilation was re-established, combining PRVC (VT: 7 mL/kg) and CNEP (-15 cmH
O) without any hyperinflation maneuver and data collection was then repeated at 5 min and 1 h. Compared to OLV, significant increases in PaO
(154.1 ± 13.3 vs. 173.8 ± 22.1) and decreases in PaCO
(52.6 ± 11.7 vs. 40.3 ± 4.5 mmHg,
< 0.05 for both) were observed 5 minutes following initiation of CNEP, and these benefits in gas exchange remained after an hour of CNEP. Gradual improvements in lung aeration in the non-collapsed lung were also detected by electrical impedance tomography (
< 0.05) after 5 and 60 min of CNEP. Hemodynamics and ventilation parameters remained stable under CNEP. Application of CNEP in the presence of whole lung atelectasis proved to be efficient in improving gas exchange via recruiting the lung without excessive airway pressures. These benefits of combined CNEP and positive pressure ventilation may have particular value in relieving atelectasis in the postoperative period of surgical procedures requiring OLV.
Although spontaneous breathing is known to exhibit substantial physiological fluctuation that contributes to alveolar recruitment, changes in the variability of the respiratory pattern following ...inhalation of carbon dioxide (CO
) and volatile anesthetics have not been characterized. Therefore, we aimed at comparing the indices of breathing variability under wakefulness, sleep, hypercapnia and sedative and anesthetic concentrations of sevoflurane.
Spontaneous breathing pattern was recorded on two consecutive days in six rabbits using open whole-body plethysmography under wakefulness and spontaneous sleep and following inhalation of 5% CO
, 2% sevoflurane (0.5 MAC) and 4% (1 MAC) sevoflurane. Tidal volume (V
), respiratory rate (RR), minute ventilation (MV), inspiratory time (T
) and mean inspiratory flow (V
/T
) were calculated from the pressure fluctuations in the plethysmograph. Means and coefficients of variation were calculated for each measured variable. Autoregressive model fitting was applied to estimate the relative contributions of random, correlated, and oscillatory behavior to the total variance.
Physiological sleep decreased MV by lowering RR without affecting V
. Hypercapnia increased MV by elevating V
. Sedative and anesthetic concentrations of sevoflurane increased V
but decreased MV due to a decrease in RR. Compared to the awake stage, CO
had no effect on V
/T
while sevoflurane depressed significantly the mean inspiratory flow. Compared to wakefulness, the variability in V
, RR, MV, T
and V
/T
were not affected by sleep but were all significantly decreased by CO
and sevoflurane. The variance of T
originating from correlated behavior was significantly decreased by both concentrations of sevoflurane compared to the awake and asleep conditions.
The variability of spontaneous breathing during physiological sleep and sevoflurane-induced anesthesia differed fundamentally, with the volatile agent diminishing markedly the fluctuations in respiratory volume, inspiratory airflow and breathing frequency. These findings may suggest the increased risk of lung derecruitment during procedures under sevoflurane in which spontaneous breathing is maintained.
Children represent a vulnerable population in which management of nociceptive pain is complex. Drug responses in children differ from adults due to age-related differences. Moreover, therapeutic ...choices are limited by the lack of indication for a number of analgesic drugs due to the challenge of conducting clinical trials in children. Furthermore the assessment of efficacy as well as tolerance may be complicated by children's inability to communicate properly. According to the World Health Organization, weak opioids such as tramadol and codeine, may be used in addition to paracetamol and ibuprofen for moderate nociceptive pain in both children and adults. However, codeine prescription has been restricted for the last 5 years in children because of the risk of fatal overdoses linked to the variable activity of cytochrome P450 (CYP) 2D6 which bioactivates codeine. Even though tramadol has been considered a safe alternative to codeine, it is well established that tramadol pharmacodynamic opioid effects, efficacy and safety, are also largely influenced by CYP2D6 activity. For this reason, the US Food and Drug Administration recently released a boxed warning regarding the use of tramadol in children. To provide safe and effective tramadol prescription in children, a personalized approach, with dose adaptation according to CYP2D6 activity, would certainly be the safest method. We therefore recommend this approach in children requiring chronic or recurrent nociceptive pain treatment with tramadol. In case of acute inpatients nociceptive pain management, prescribing tramadol at the minimal effective dose, in a child appropriate dosage form and after clear instructions are given to the parents, remains reasonable based on current data. In all other situations, morphine should be preferred for moderate to severe nociceptive pain conditions.
Abstract
Background
Although high-frequency percussive ventilation (HFPV) improves gas exchange, concerns remain about tissue overdistension caused by the oscillations and consequent lung damage. We ...compared a modified percussive ventilation modality created by superimposing high-frequency oscillations to the conventional ventilation waveform during expiration only (eHFPV) with conventional mechanical ventilation (CMV) and standard HFPV.
Methods
Hypoxia and hypercapnia were induced by decreasing the frequency of CMV in New Zealand White rabbits (n = 10). Following steady-state CMV periods, percussive modalities with oscillations randomly introduced to the entire breathing cycle (HFPV) or to the expiratory phase alone (eHFPV) with varying amplitudes (2 or 4 cmH
2
O) and frequencies were used (5 or 10 Hz). The arterial partial pressures of oxygen (PaO
2
) and carbon dioxide (PaCO
2
) were determined. Volumetric capnography was used to evaluate the ventilation dead space fraction, phase 2 slope, and minute elimination of CO
2
. Respiratory mechanics were characterized by forced oscillations.
Results
The use of eHFPV with 5 Hz superimposed oscillation frequency and an amplitude of 4 cmH
2
O enhanced gas exchange similar to those observed after HFPV. These improvements in PaO
2
(47.3 ± 5.5 vs. 58.6 ± 7.2 mmHg) and PaCO
2
(54.7 ± 2.3 vs. 50.1 ± 2.9 mmHg) were associated with lower ventilation dead space and capnogram phase 2 slope, as well as enhanced minute CO
2
elimination without altering respiratory mechanics.
Conclusions
These findings demonstrated improved gas exchange using eHFPV as a novel mechanical ventilation modality that combines the benefits of conventional and small-amplitude high-frequency oscillatory ventilation, owing to improved longitudinal gas transport rather than increased lung surface area available for gas exchange.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This review highlights the requirements for harmonization of training, certification and continuous professional development and discusses the implications for anesthesia management of children in ...Europe.
A large prospective cohort study, Anaesthesia PRactice In Children Observational Trial (APRICOT), revealed a high incidence of perioperative severe critical events and a large variability of anesthesia practice across 33 European countries. Relevantly, quality improvement programs have been implemented in North America, which precisely define the requirements to manage anesthesia care for children. These programs, with the introduction of an incident-reporting system at local and national levels, could contribute to the improvement of anesthesia care for children in Europe.
The main factors that likely contributed to the APRICOT study results are discussed with the goal of defining clear requirement guidelines for anesthetizing children. Emphasis is placed on the importance of an incident-reporting system that can be used for both competency-based curriculum for postgraduate training as well as for continuous professional development. Variability in training as well as in available resources, equipment and facilities limit the generalization of some of the APRICOT results. Finally, the impact on case outcome of the total number of pediatric cases attended by the anesthesiologist should be taken into consideration along with the level of expertise of the anesthesiologist for complex pediatric anesthesia cases.
Introducing mathematically derived variability (MVV) into the otherwise monotonous conventional mechanical ventilation has been suggested to improve lung recruitment and gas exchange. Although the ...application of a ventilation pattern based on variations in physiological breathing (PVV) is beneficial for healthy lungs, its value in the presence of acute respiratory distress syndrome (ARDS) has not been characterized. We therefore aimed at comparing conventional pressure-controlled ventilation with (PCS) or without regular sighs (PCV) to MVV and PVV at two levels of positive end-expiratory pressure (PEEP) in a model of severe ARDS.
Anesthetised rabbits (
= 54) were mechanically ventilated and severe ARDS (PaO
/FiO
≤ 150 mmHg) was induced by combining whole lung lavage, i.v. endotoxin and injurious ventilation. Rabbits were then randomly assigned to be ventilated with PVV, MVV, PCV, or PCS for 5 h while maintaining either 6 or 9 cmH
O PEEP. Ventilation parameters, blood gas indices and respiratory mechanics (tissue damping, G, and elastance, H) were recorded hourly. Serum cytokine levels were assessed with ELISA and lung histology was analyzed.
Although no progression of lung injury was observed after 5 h of ventilation at PEEP 6 cmH
O with PVV and PCV, values for G (58.8 ± 71.1half-width of 95% CI% and 40.8 ± 39.0%, respectively), H (54.5 ± 57.2%, 50.7 ± 28.3%), partial pressure of carbon-dioxide (PaCO
, 43.9 ± 23.8%, 46.2 ± 35.4%) and pH (-4.6 ± 3.3%, -4.6 ± 2.2%) worsened with PCS and MVV. Regardless of ventilation pattern, application of a higher PEEP improved lung function and precluded progression of lung injury and inflammation. Histology lung injury scores were elevated in all groups with no difference between groups at either PEEP level.
At moderate PEEP, variable ventilation based on a pre-recorded physiological breathing pattern protected against progression of lung injury equally to the conventional pressure-controlled mode, whereas mathematical variability or application of regular sighs caused worsening in lung mechanics. This outcome may be related to the excessive increases in peak inspiratory pressure with the latter ventilation modes. However, a greater benefit on respiratory mechanics and gas exchange could be obtained by elevating PEEP, compared to the ventilation mode in severe ARDS.
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