The latest medical research on Anesthesiology
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Impact of the World Health Organization Surgical Safety Checklist on Patient Safety.Anesthesiology
The incidence of surgical complications has remained largely unchanged over the past two decades. Inherent complexity in surgery, new technology po...
Breathing under Anesthesia: A Key Role for the Retrotrapezoid Nucleus Revealed by Conditional Phox2b Mutant Mice.Anesthesiology
Many if not all drugs used in anesthesia and analgesia can produce potentially severe respiratory depressionMaintenance of breathing under anesthesia is linked to the drive exerted by the retrotrapezoid nucleus on the respiratory central pattern generatorThe retrotrapezoid nucleus neurons that stimulate breathing during anesthesia are carbon dioxide-sensitive noncatecholaminergic neurons that express Phox2b, a master gene for the development of autonomic neuronsThe conditional mouse model with the +7Ala repeat mutation targeted to the retrotrapezoid nucleus (Phox2b mice) present a massive selective loss of retrotrapezoid nucleus neurons and lack carbon dioxide chemosensitivity at birth but survive normally and partially recover carbon dioxide chemosensitivity in adulthood WHAT THIS ARTICLE TELLS US THAT IS NEW: Ketamine, propofol, and fentanyl caused lethal respiratory failure in most mice with selective genetic loss of retrotrapezoid nucleus neurons, at doses that were safe in their wild type littermates BACKGROUND:: Optimal management of anesthesia-induced respiratory depression requires identification of the neural pathways that are most effective in maintaining breathing during anesthesia. Lesion studies point to the brainstem retrotrapezoid nucleus. We therefore examined the respiratory effects of common anesthetic/analgesic agents in mice with selective genetic loss of retrotrapezoid nucleus neurons (Phox2b mice, hereafter designated "mutants").
All mice received intraperitoneal ketamine doses ranging from 100 mg/kg at postnatal day (P) 8 to 250 mg/kg at P60 to P62. Anesthesia effects in P8 and P14 to P16 mice were then analyzed by administering propofol (100 and 150 mg/kg at P8 and P14 to P16, respectively) and fentanyl at an anesthetic dose (1 mg/kg at P8 and P14 to P16).
Most mutant mice died of respiratory arrest within 13 min of ketamine injection at P8 (12 of 13, 92% vs. 0 of 8, 0% wild type; Fisher exact test, P < 0.001) and P14 to P16 (32 of 42, 76% vs. 0 of 59, 0% wild type; P < 0.001). Cardiac activity continued after terminal apnea, and mortality was prevented by mechanical ventilation, supporting respiratory arrest as the cause of death in the mutants. Ketamine-induced mortality in mutants compared to wild types was confirmed at P29 to P31 (24 of 36, 67% vs. 9 of 45, 20%; P < 0.001) and P60 to P62 (8 of 19, 42% vs. 0 of 12, 0%; P = 0.011). Anesthesia-induced mortality in mutants compared to wild types was also observed with propofol at P8 (7 of 7, 100% vs. 0 of 17,7/7, 100% vs. 0/17, 0%; P < 0.001) and P14 to P16 (8 of 10, 80% vs. 0 of 10, 0%; P < 0.001) and with fentanyl at P8 (15 of 16, 94% vs. 0 of 13, 0%; P < 0.001) and P14 to P16 (5 of 7, 71% vs. 0 of 11, 0%; P = 0.002).
Ketamine, propofol, and fentanyl caused death by respiratory arrest in most mice with selective loss of retrotrapezoid nucleus neurons, in doses that were safe in their wild type littermates. The retrotrapezoid nucleus is critical to sustain breathing during deep anesthesia and may prove to be a pharmacologic target for this purpose.
Dextromethorphan Analgesia in a Human Experimental Model of Hyperalgesia.Anesthesiology
Neuropathic pain, which presents abnormal pain manifestations including allodynia and hyperalgesia, is associated with central sensitization involving N-methyl-D-aspartate receptorsIn the freeze-injury hyperalgesia model, a cold burn leads to development of both primary hyperalgesia and secondary hyperalgesia, which develops away from the site of injury without apparent tissue modification, and is associated with central sensitization and activation of N-methyl-D-aspartate receptors in the spinal cordDextromethorphan, which is an N-methyl-D-aspartate receptor antagonist, is antihyperalgesic in preclinical pain models WHAT THIS ARTICLE TELLS US THAT IS NEW: Using the freeze-injury pain model in a randomized, double-blind, placebo-controlled crossover trial of 30-mg doses of oral dextromethorphan in 20 male volunteers, dextromethorphan was antihyperalgesic and reversed peripheral and central neuronal sensitizationBecause dextromethorphan had no intrinsic antinociceptive effect in acute pain on healthy skin, N-methyl-D-aspartate receptors may need to be sensitized by pain for dextromethorphan to be effective BACKGROUND:: Central pain sensitization is often refractory to drug treatment. Dextromethorphan, an N-methyl-D-aspartate receptor antagonist, is antihyperalgesic in preclinical pain models. The hypothesis is that dextromethorphan is also antihyperalgesic in humans.
This randomized, double-blind, placebo-controlled, crossover study explores the antihyperalgesic effect of single and repeated 30-mg dose of oral dextromethorphan in 20 volunteers, using the freeze-injury pain model. This model leads to development of primary and secondary hyperalgesia, which develops away from the site of injury and is associated with central sensitization and activation of N-methyl-D-aspartate receptor in the spinal cord. The primary outcome was antihyperalgesia calculated with the area under the curve of the percentage change in mechanical pain threshold (electronic von Frey) on the area of secondary hyperalgesia. The secondary outcomes were mechanical pain threshold on the area of primary hyperalgesia and cognitive (reaction time) effect.
Single 30-mg results are reported. Antihyperalgesia (% · min) is significantly higher on the area of secondary hyperalgesia with dextromethorphan than placebo (median [interquartile range]: 3,029 [746; 6,195] vs. 710 [-3,248; 4,439], P = 0.009, Hedge's g = 0.8, 95% CI [0.1; 1.4]). On primary hyperalgesia area, mechanical pain threshold 2 h after drug intake is significantly higher with dextromethorphan (P = 0.011, Hedge's g = 0.63, 95% CI [0.01; 1.25]). No difference in antinociception is observed after thermal painful stimuli on healthy skin between groups. Reaction time (ms) is shorter with placebo than with dextromethorphan (median [interquartile range]: 21.6 [-37.4; 0.1] vs. -1.2 [-24.3; 15.4], P = 0.015, Hedge's g = 0.75, 95% CI [0.12; 1.39]). Nonserious adverse events occurrence (15%, 3 of 20 volunteers) was similar in both groups.
This study shows that low-dose (30-mg) dextromethorphan is antihyperalgesic in humans on the areas of primary and secondary hyperalgesia and reverses peripheral and central neuronal sensitization. Because dextromethorphan had no intrinsic antinociceptive effect in acute pain on healthy skin, N-methyl-D-aspartate receptor may need to be sensitized by pain for dextromethorphan to be effective.
Measuring Childbirth Outcomes Using Administrative and Birth Certificate Data.Anesthesiology
Maternal complications during and after childbirth demonstrate wide variation across hospitalsNational reporting systems do not integrate maternal and newborn outcomes when defining hospital obstetric care quality WHAT THIS ARTICLE TELLS US THAT IS NEW: Administrative data can be used to calculate hospital-level risk-adjusted maternal, newborn, and composite maternal-newborn performanceMaternal and newborn hospital performance were poorly correlated, suggesting that composite performance measures must also report underlying maternal and newborn performance separately BACKGROUND:: The number of pregnancy-related deaths and severe maternal complications continues to rise in the United States, and the quality of obstetrical care across U.S. hospitals is uneven. Providing hospitals with performance feedback may help reduce the rates of severe complications in mothers and their newborns. The aim of this study was to develop a risk-adjusted composite measure of severe maternal morbidity and severe newborn morbidity based on administrative and birth certificate data.
This study was conducted using linked administrative data and birth certificate data from California. Hierarchical logistic regression prediction models for severe maternal morbidity and severe newborn morbidity were developed using 2011 data and validated using 2012 data. The composite metric was calculated using the geometric mean of the risk-standardized rates of severe maternal morbidity and severe newborn morbidity.
The study was based on 883,121 obstetric deliveries in 2011 and 2012. The rates of severe maternal morbidity and severe newborn morbidity were 1.53% and 3.67%, respectively. Both the severe maternal morbidity model and the severe newborn models exhibited acceptable levels of discrimination and calibration. Hospital risk-adjusted rates of severe maternal morbidity were poorly correlated with hospital rates of severe newborn morbidity (intraclass correlation coefficient, 0.016). Hospital rankings based on the composite measure exhibited moderate levels of agreement with hospital rankings based either on the maternal measure or the newborn measure (κ statistic 0.49 and 0.60, respectively.) However, 10% of hospitals classified as average using the composite measure had below-average maternal outcomes, and 20% of hospitals classified as average using the composite measure had below-average newborn outcomes.
Maternal and newborn outcomes should be jointly reported because hospital rates of maternal morbidity and newborn morbidity are poorly correlated. This can be done using a childbirth composite measure alongside separate measures of maternal and newborn outcomes.
Midazolam Sedation Induces Upper Limb Coordination Deficits That Are Reversed by Flumazenil in Patients with Eloquent Area Gliomas.Anesthesiology
Sedation is known to unmask focal neurologic deficits in patients with supratentorial brain tumors but the mechanism is unclear WHAT THIS ARTICLE TELLS US THAT IS NEW: When induced with midazolam, these deficits can be reversed by flumazenil, suggesting a γ-aminobutyric acid-mediated mechanism BACKGROUND:: Midazolam has been found to exacerbate or unmask limb motor dysfunction in patients with brain tumors. This study aimed to determine whether the exacerbated upper limb motor-sensory deficits are mediated through benzodiazepine sites by demonstrating reversibility by flumazenil in patients with gliomas in eloquent areas.
This was an interventional, parallel assignment, nonrandomized trial. Study subjects were admitted in the operating room. Patients with supratentorial eloquent area gliomas and volunteers of similar age without neurologic disease were sedated with midazolam, but still responsive and cooperative. Motor and sensory functions for upper extremities were evaluated by the Nine-Hole Peg Test before and after midazolam, as well as after flumazenil reversal.
Thirty-two cases were included: 15 in the glioma group and 17 in the control group. The total dose of midazolam and flumazenil were comparable between the groups. In the glioma group, the times to task completion after midazolam in the contralateral hand (P = 0.001) and ipsilateral hand (P = 0.002) were 26.5 (95% CI, 11.3 to 41.7) and 13.7 (95% CI, 5.0 to 22.4) seconds slower than baseline, respectively. After flumazenil reversal, the contralateral hand (P = 0.99) and ipsilateral hand (P = 0.187) performed 1.2 (95% CI, -3.3 to 5.8) and 1.5 (95% CI, -0.5 to 3.5) seconds slower than baseline, respectively. In the control group, the dominant (P < 0.001) and nondominant hand (P = 0.006) were 2.9 (95% CI, 1.4 to 4.3) and 1.7 (95% CI, 0.5 to 2.9) seconds slower than baseline, respectively. After flumazenil, the dominant hand (P = 0.99) and nondominant hand (P = 0.019) performed 0.2 (95% CI, -0.7 to 1.0) and 1.3 (95% CI, -0.2 to 2.4) seconds faster than baseline, respectively.
In patients with eloquent area gliomas, mild sedation with midazolam induced motor coordination deficits in upper limbs. This deficit was almost completely reversed by the benzodiazepine antagonist flumazenil, suggesting that this is a reversible abnormality linked to occupation of the receptor by midazolam.
Short-term Physiologic Consequences of Regional Pulmonary Vascular Occlusion in Pigs.Anesthesiology
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- what this article tells us that is new
After pulmonary artery occlusion (mimicking a pulmonary embolism), perfusion is redistributed to the rest of the lung tissue, but the distribution of ventilation is uncertain.
Data from anesthetized pigs (uninjured lungs) indicates that the perfusion is redistributed as suspected. Similarly, ventilation is redistributed from nonperfused to perfused lung tissue. This limits the increase in dead space and is accompanied by less density in the occluded lung.
Acute unilateral pulmonary arterial occlusion causes ventilation-perfusion mismatch of the affected lung area. A diversion of ventilation from nonperfused to perfused lung areas, limiting the increase in dead space, has been described. The hypothesis was that the occlusion of a distal branch of the pulmonary artery would cause local redistribution of ventilation and changes in regional lung densitometry as assessed with quantitative computed tomography.
In eight healthy, anesthetized pigs (18.5 ± 3.8 kg) ventilated with constant ventilatory settings, respiratory mechanics, arterial blood gases, and quantitative computed tomography scans were recorded at baseline and 30 min after the inflation of the balloon of a pulmonary artery catheter. Regional (left vs. right lung and perfused vs. nonperfused area) quantitative computed tomography was performed.
The balloon always occluded a branch of the left pulmonary artery perfusing approximately 30% of lung tissue. Physiologic dead space increased (0.37 ± 0.17 vs. 0.43 ± 0.17, P = 0.005), causing an increase in PaCO2 (39.8 [35.2 to 43.0] vs. 41.8 [37.5 to 47.1] mmHg, P = 0.008) and reduction in pH (7.46 [7.42 to 7.50] vs. 7.42 [7.38 to 7.47], P = 0.008). Respiratory system compliance was reduced (24.4 ± 4.2 vs. 22.8 ± 4.8 ml · cm H2O, P = 0.028), and the reduction was more pronounced in the left hemithorax. Quantitative analysis of the nonperfused lung area revealed a significant reduction in lung density (-436 [-490 to -401] vs. -478 [-543 to -474] Hounsfield units, P = 0.016), due to a reduction in lung tissue (90 ± 23 vs. 81 ± 22 g, P < 0.001) and an increase in air volume (70 ± 22 vs. 82 ± 26 ml, P = 0.022).
Regional pulmonary vascular occlusion is associated with a diversion of ventilation from nonperfused to perfused lung areas. This compensatory mechanism effectively limits ventilation perfusion mismatch. Quantitative computed tomography documented acute changes in lung densitometry after pulmonary vascular occlusion. In particular, the nonperfused lung area showed an increase in air volume and reduction in tissue mass, resulting in a decreased lung density.
Atrophy of Diaphragm and Pectoral Muscles in Critically Ill Patients.Anesthesiology
- what we already know about this topic
- what this article tells us that is new
Muscle atrophy is common in the critically ill, and diaphragm atrophy occurs during mechanical ventilation. It is not known whether wasting of diaphragm and nondiaphragm muscle is related.
Ultrasound was used for serial assessment of diaphragm and pectoral muscle in 97 critically ill patients. Diaphragm and pectoral atrophy occurred in 48% and 29%, respectively, and was associated with septic shock (diaphragm) and steroid use (pectoral); atrophy of the two muscle types appears unrelated.
Muscle atrophy occurs early during critical illnesses. Although diffuse, this atrophy may specifically affect the diaphragm under artificial inactivity accompanying invasive mechanical ventilation. The primary objective of this study was to highlight diaphragm atrophy during the first 5 days of critical illness. Monitoring of pectoral thickness (a nonpostural muscle with mainly phasic function) served as a control.
Diaphragm and pectoral thicknesses were measured by ultrasound within the first 24 h of admission in 97 critically ill patients, including 62 on mechanical ventilation. Thirty-five patients were reexamined at day 5.
Baseline median (interquartile) values of diaphragm and pectoral thicknesses at day 1 were 2.4 (2.0, 2.9) and 5.9 (4.7, 7.2) mm, respectively (n = 97). Higher values of diaphragm thickness at baseline were positively associated with male sex, chronic obstructive pulmonary disease, and diabetes. Diaphragm and pectoral atrophies (defined as a decrease of 10% or more between day 1 and day 5) were detected in 48% (17 of 35) and 29% (10 of 34) respectively, and were uncorrelated with each other. Diaphragm atrophy was significantly more frequent in patients with septic shock and in those with mechanical ventilation, as compared with their respective counterparts (71% [10 of 14] vs. 33% [7 of 21], P = 0.027 and 71% [17 of 28] vs. 0% [0 of 7], P = 0.004, respectively), whereas pectoral atrophy was more common in patients treated with steroids as compared with their counterparts (58% [7 of 12] vs. 14% [3 of 22], P = 0.006). A statistically significant association between diaphragm atrophy and outcome was not found. Pectoral atrophy seemed associated with less successful weaning from mechanical ventilation at day 14 (12% [1 of 8] vs. 58% [11 of 19], P = 0.043).
Ultrasound enables identification of specific early diaphragm atrophy that affects the majority of mechanically ventilated patients and septic shock patients. Diaphragm atrophy and pectoral muscle atrophy seem to be two unrelated processes.
Days Alive and Out of Hospital: Validation of a Patient-centered Outcome for Perioperative Medicine.Anesthesiology
Days alive and out of hospital is an easily obtained patient-centered outcome WHAT THIS ARTICLE TELLS US THAT IS NEW: Days alive and out of hospital was associated with patient-level factors including comorbidities, advanced age, and complications, but not less relevant hospital-level factorsIt appears to be a useful measure of surgical impact BACKGROUND:: Days alive and out of hospital is a potentially useful patient-centered quality measure for perioperative care in adult surgical patients. However, there has been very limited prior validation of this endpoint with respect to its ability to capture differences in patient-level risk factor profiles and longer-term postoperative outcomes. The main objective of this study was assessment of the feasibility and validity of days alive and out of hospital as a patient-centered outcome for perioperative medicine.
The authors evaluated 540,072 adults undergoing 1 of 12 major elective noncardiac surgical procedures between 2006 to 2014. Primary outcome was days alive and out of hospital at 30 days, secondary outcomes were days alive and out of hospital at 90 days and 180 days. Unadjusted and risk-adjusted adjusted analyses were used to determine the association of days alive and out of hospital with patient-, surgery-, and hospital-level characteristics. Patients with days alive and out of hospital at 30 days values less than the tenth percentile were also classified as having poor days alive and out of hospital at 30 days. The authors then determined the association of poor days alive and out of hospital at 30 days with in-hospital complications, poor days alive and out of hospital at 90 days (less than the tenth percentile), and poor days alive and out of hospital at 180 days (less than the tenth percentile).
Overall median (interquartile range) days alive and out of hospital at 30, 90, and 180 days were 26 (24 to 27), 86 (84 to 87), and 176 (173 to 177) days, respectively. Median days alive and out of hospital at 30 days was highest for hysterectomy and endovascular aortic aneurysm repair (27 days) and lowest for upper gastrointestinal surgery (22 days). Days alive and out of hospital at 30 days was associated with clinically sensible patient-level factors (comorbidities, advanced age, postoperative complications), but not measured hospital-level factors (academic status, bed size). Of patients with good days alive and out of hospital at 30 days, 477,163 of 486,087 (98%) and 470,093 of 486,087 (97%) remained within this group (greater than the tenth percentile) at days alive and out of hospital at 90 and 180 days.
Days alive and out of hospital is a feasibly measured patient-centered outcome that is associated with clinically sensible patient characteristics, surgical complexity, in-hospital complications, and longer-term outcomes. Days alive and out of hospital forms a novel patient-centered outcome for future clinical trials and observational studies for adult surgical patients.
Lung Pharmacokinetics of Tobramycin by Intravenous and Nebulized Dosing in a Mechanically Ventilated Healthy Ovine Model.Anesthesiology
For most bacterial pneumonia, the lung interstitium is considered to be the site of infection, and adequate antibiotic concentrations are important for drug effectDespite systemic antibiotic therapy, therapeutic failure is common, perhaps due to poor lung penetration, and resulting low interstitial space fluid antibiotic concentrationsIncreasing systemic antibiotic doses in order to increase interstitial space fluid antibiotic concentrations could lead to toxicities such as nephrotoxicity WHAT THIS ARTICLE TELLS US THAT IS NEW: In a mechanically ventilated healthy large animal model, nebulized tobramycin produced higher peak lung interstitial space fluid concentrations, as well as higher initial epithelial lining fluid concentrations, with lower plasma concentrations than were observed after intravenous administration due to more extensive lung penetration BACKGROUND:: Nebulized antibiotics may be used to treat ventilator-associated pneumonia. In previous pharmacokinetic studies, lung interstitial space fluid concentrations have never been reported. The aim of the study was to compare intravenous and nebulized tobramycin concentrations in the lung interstitial space fluid, epithelial lining fluid, and plasma in mechanically ventilated sheep with healthy lungs.
Ten anesthetized and mechanically ventilated healthy ewes underwent surgical insertion of microdialysis catheters in upper and lower lobes of both lungs and the jugular vein. Five ewes were given intravenous tobramycin 400 mg, and five were given nebulized tobramycin 400 mg. Microdialysis samples were collected every 20 min for 8 h. Bronchoalveolar lavage was performed at 1 and 6 h.
The peak lung interstitial space fluid concentrations were lower with intravenous tobramycin 20.2 mg/l (interquartile range, 12 mg/l, 26.2 mg/l) versus the nebulized route 48.3 mg/l (interquartile range, 8.7 mg/l, 513 mg/l), P = 0.002. For nebulized tobramycin, the median epithelial lining fluid concentrations were higher than the interstitial space fluid concentrations at 1 h (1,637; interquartile range, 650, 1,781, vs. 16 mg/l, interquartile range, 7, 86, P < 0.001) and 6 h (48, interquartile range, 17, 93, vs. 4 mg/l, interquartile range, 2, 9, P < 0.001). For intravenous tobramycin, the median epithelial lining fluid concentrations were lower than the interstitial space fluid concentrations at 1 h (0.19, interquartile range, 0.11, 0.31, vs. 18.5 mg/l, interquartile range, 9.8, 23.4, P < 0.001) and 6 h (0.34, interquartile range, 0.2, 0.48, vs. 3.2 mg/l, interquartile range, 0.9, 4.4, P < 0.001).
Compared with intravenous tobramycin, nebulized tobramycin achieved higher lung interstitial fluid and epithelial lining fluid concentrations without increasing systemic concentrations.
Positive End-expiratory Pressure and Postoperative Atelectasis: A Randomized Controlled Trial.Anesthesiology
- what we already know about this topic
- what this article tells us that is new
Positive end-expiratory pressure (PEEP) is used during anesthesia to prevent atelectasis, but its impact during emergence from anesthesia is uncertain.
Thirty patients undergoing nonabdominal surgery under general anesthesia were randomized to maintained (7 or 9 cm H2O) or zero PEEP before being given 100% oxygen for emergence preoxygenation. Postoperative atelectasis (assessed by computed tomography) was small with no effect on oxygenation, whether or not PEEP was used during emergence.
Positive end-expiratory pressure (PEEP) increases lung volume and protects against alveolar collapse during anesthesia. During emergence, safety preoxygenation preparatory to extubation makes the lung susceptible to gas absorption and alveolar collapse, especially in dependent regions being kept open by PEEP. We hypothesized that withdrawing PEEP before starting emergence preoxygenation would limit postoperative atelectasis formation.
This was a randomized controlled evaluator-blinded trial in 30 healthy patients undergoing nonabdominal surgery under general anesthesia and mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index. A computed tomography scan at the end of surgery assessed baseline atelectasis. The study subjects were thereafter allocated to either maintained PEEP (n = 16) or zero PEEP (n = 14) during emergence preoxygenation. The primary outcome was change in atelectasis area as evaluated by a second computed tomography scan 30 min after extubation. Oxygenation was assessed by arterial blood gases.
Baseline atelectasis was small and increased modestly during awakening, with no statistically significant difference between groups. With PEEP applied during awakening, the increase in atelectasis area was median (range) 1.6 (-1.1 to 12.3) cm and without PEEP 2.3 (-1.6 to 7.8) cm. The difference was 0.7 cm (95% CI, -0.8 to 2.9 cm; P = 0.400). Postoperative atelectasis for all patients was median 5.2 cm (95% CI, 4.3 to 5.7 cm), corresponding to median 2.5% of the total lung area (95% CI, 2.0 to 3.0%). Postoperative oxygenation was unchanged in both groups when compared to oxygenation in the preoperative awake state.
Withdrawing PEEP before emergence preoxygenation does not reduce atelectasis formation after nonabdominal surgery. Despite using 100% oxygen during awakening, postoperative atelectasis is small and does not affect oxygenation, possibly conditional on an open lung during anesthesia, as achieved by intraoperative PEEP.
Stress, burnout, depression and work satisfaction among UK anaesthetic trainees: a qualitative analysis of in-depth participant interviews in the Satisfaction and Wellbeing in Anaesthetic Training study.Anaesthesia
Anaesthetists experience unique stressors, and recent evidence suggests a high prevalence of stress and burnout in trainee anaesthetists. There has...
Removal methods of rigid stylets to minimise adverse force and tracheal tube movement: a mathematical and in-vitro analysis in manikins.Anaesthesia
This study investigated displacement of the tracheal tube caused by different methods of intubating stylet removal, using in-vitro experiments and ...