Sex-related Differences in Loop Gain during High-Altitude Sleep-disordered Breathing.

Rationale: Central sleep apnea (CSA) is pervasive during sleep at high altitude, disproportionately impacting men and associated with increased peripheral chemosensitivity. Objectives: We aimed to assess whether biological sex affects loop gain (LGn) and CSA severity during sleep over 9-10 days of acclimatization to 3,800 m. We hypothesized that CSA severity would worsen with acclimatization in men but not in women because of greater increases in LGn in men. Methods: Sleep studies were collected from 20 (12 male) healthy participants at low altitude (1,130 m, baseline) and after ascent to (nights 2/3, acute) and residence at high altitude (nights 9/10, prolonged). CSA severity was quantified as the respiratory event index (REI) as a surrogate of the apnea-hypopnea index. LGn, a measure of ventilatory control instability, was quantified using a ventilatory control model fit to nasal flow. Linear mixed models evaluated effects of time at altitude and sex on respiratory event index and LGn. Data are presented as contrast means with 95% confidence intervals. Results: REI was comparable between men and women at acute altitude (4.1 [-9.3, 17.5] events/h; P = 0.54) but significantly greater in men at prolonged altitude (23.7 [10.3, 37.1] events/h; P = 0.0008). Men had greater LGn than did women for acute (0.08 [0.001, 0.15]; P = 0.047) and prolonged (0.17 [0.10, 0.25]; P < 0.0001) altitude. The change in REI per change in LGn was significantly greater in men than in women (107 ± 46 events/h/LGn; P = 0.02). Conclusions: The LGn response to high altitude differed between sexes and contributed to worsening of CSA over time in men but not in women. This sex difference in acclimatization appears to protect females from high altitude-related CSA. These data provide fundamental sex-specific physiological insight into high-altitude acclimatization in healthy individuals and may help to inform sex differences in sleep-disordered breathing pathogenesis in patients with cardiorespiratory disease.

Evaluation of a novel emergency front of neck access device in a benchtop model of obesity.

BACKGROUND: Emergency front of neck access (eFONA) is a critical step in oxygenation in cases of unrelieved airway obstruction. Multiple techniques are used in clinical practice without agreement regarding the optimal approach. We evaluated a novel device, the Cric-Guide (CG), a channelled bougie introducer that enters the airway in a single action and compared it with a scalpel-bougie-tube (SBT) technique in laboratory benchtop model. METHODS: Seven anaesthesiologists attempted eFONA on both obese and non-obese models using both techniques in randomized order on an excised porcine trachea with an intact larynx with variable subcutaneous tissue depth. The primary outcome was successful tracheal cannulation. Secondary outcomes included false passage rate, time and tissue injury. RESULTS: Anaesthesiologists performed 4 cricothyroidotomies on each model with each device. The CG was more successful in airway cannulation (47/56 [89.4%] vs. 33/56 [58.9%], P = 0.007). This difference was observed in the obese model only. The CG was associated with fewer false passages than the standard technique in the obese model (8/56 [14.3%] vs. 23/56 [41.1%], P = 0.006). There were no significant differences in time to completion or injury patterns between the techniques in the obese model, but the SBT was faster in the non-obese model. There was no difference in the proportion of specimens injured. CONCLUSION: The Cric-Guide device was more successful than the standard SBT technique in airway cannulation in an obese neck model and with equivalent frequency and distribution of injury but performed equivalently in the non-obese model.

Accuracy of pediatric cricothyroid membrane identification by digital palpation and implications for emergency front of neck access.

BACKGROUND: Emergency front of neck access in a "can't intubate can't oxygenate" scenario in pediatrics is rare. Ideally airway rescue would involve the presence of an ear, nose, and throat surgeon. If unavailable however, responsibility lies with the anesthesiologist and accurate identification of anterior neck structures is essential for success. AIM: We assessed anesthesiologists' accuracy in identification of the pediatric cricothyroid membrane by digital palpation in three predefined age groups (37 weeks to <1 year old, 1-8 years old, and 9-16 years old) and whether accuracy improved with repetition. We also investigated a novel hypothetical vertical skin incision strategy to successfully expose the cricothyroid membrane. METHODS: We asked anesthesiologists to identify the location of the cricothyroid membrane of anesthetized children in the extended neck position. Accuracy was defined as a mark made within the margins of the cricothyroid membrane using ultrasound as a reference standard. The position of the cricothyroid membrane relative to the neck midpoint, between the suprasternal notch and mentum, was defined for each child. Using this neck midpoint, we determined the hypothetical vertical skin incision lengths required to successfully expose the cricothyroid membrane ("midpoint incision"). RESULTS: Ninety-seven patients were included in this study. There were 14, 58, and 25 patients recruited across the three predefined groups. Accurate anesthesiologist identification of the location of the cricothyroid membrane occurred in 29.4%, 28.6%, and 38.2% of attempts, respectively. The majority of inaccurate assessments (64.1%) were below the cricothyroid membrane. There was no improvement in accuracy with repetition. Hypothetical "midpoint incision" lengths of 20, 30, and 35 mm were required. CONCLUSION: Significant anesthesiologist inaccuracy exists in locating the cricothyroid membrane in children of all ages. This has implications for the technical approach to emergency front of neck access and how we teach the management of "can't intubate can't oxygenate" in pediatric practice.

Accuracy of ultrasound in measurement of the pediatric cricothyroid membrane.

BACKGROUND: Emergency front of neck airway is a recommended airway rescue strategy in children over 1 year old. Surgical tracheostomy is advocated as the first-line technique, but in the absence of an ear, nose and throat surgeon cricothyroidotomy or tracheostomy is proposed. Recent research shows that clinical identification of the cricothyroid membrane is frequently inaccurate in older children and adults and has prompted investigation of ultrasound as a potential clinical tool for emergency front of neck airway. Advance knowledge of the dimensions of the pediatric cricothyroid membrane may assist clinicians in determining the feasibility of emergency front of neck airway, optimum technique, and equipment. AIMS: The aim of this study was to assess the accuracy of ultrasound-assisted pediatric cricothyroid membrane localization and dimension measurement using magnetic resonance imaging as the reference standard. METHODS: After structured training, two pediatric anesthesiology trainees used ultrasound to identify and measure the dimensions of the cricothyroid membrane in pediatric patients undergoing elective magnetic resonance imaging of the head and neck under general anesthesia. A pediatric radiologist reviewed the corresponding magnetic resonance imaging scans and measured the height of the cricothyroid membrane. The accuracy of the cricothyroid membrane height as measured by ultrasound was compared to that measured by magnetic resonance imaging. RESULTS: Twenty-two patients were included in the study. The cricothyroid membrane was accurately identified by ultrasound in all cases. The correlation coefficient for cricothyroid membrane height measured by ultrasound and that measured by magnetic resonance imaging was 0.98 (95% C.I 0.95-0.99, P < 0.0001). The bias was -0.16 mm and the precision was 0.19 mm. All differences were within the a priori limits of agreement. The 95% limits of agreement were -0.54 to 0.22 mm. CONCLUSION: Ultrasound can be used to accurately identify and measure cricothyroid membrane height in pediatric patients. This approach could have clinical and research utility.

Achieving proficiency in rigid bronchoscopy-a study in manikins.

BACKGROUND: Rigid bronchoscopy may be used to relieve acute airway obstruction following induction of anaesthesia and is a recommended option for management of the difficult airway. The ability of anaesthetists to perform rigid bronchoscopy has not been reported. We sought to explore the acquisition of procedural skill in rigid bronchoscopy by anaesthesiologists in a manikin. METHODS: In a prospective interventional study, participants were asked to perform 40 rigid bronchoscopies in a TruCorp AirSim Advance airway manikin, configured to a randomised sequence of easy or difficult laryngoscopic grades to which the participants were blinded. The primary outcome was stabilisation (the attempt after which no further reduction in procedural time occurred). Dental injury and oesophageal intubation were also recorded. Forty anaesthesiologists and 40 unskilled controls (without laryngoscopic skills) participated. RESULTS: In the easy model, stabilisation occurred at attempt 8 in the anaesthesiology group and 10 in the unskilled controls. In the difficult model, stabilisation occurred at attempt 10 in both groups. Dental injury was less common in the anaesthesiology group. The proportion of participants achieving procedural competency did not differ between groups in either the easy (35/40 vs. 30/40) or difficult model (32/40 vs. 25/40). CONCLUSIONS: This study shows that the technical skill of rigid bronchoscopy can be acquired within 10 repetitions in a manikin model. As procedural competence and complication frequency vary with the laryngoscopic grade of the model, both easy and difficult configurations should be used for training. Advanced laryngoscopic skills are not required prior to training in this technique.

The use of pain relief during labor among migrant obstetric populations.

OBJECTIVE: To identify patterns in intrapartum analgesia use in the migrant obstetric population. METHODS: A retrospective analysis included all deliveries with neonates above 500g in weight at a university hospital in Dublin, Ireland between 2009 and 2013. Analgesia was classified as neuraxial or non-neuraxial. Parturients were excluded owing to missing data, elective cesarean deliveries, and the use of analgesia during treatment for obstetric complications. RESULTS: There were 36 689 deliveries included in the present study. Increased odds of not using neuraxial analgesia during delivery were observed among migrant parturients from North Africa, Sub-Saharan Africa, the Far East, India, and Eastern Europe compared with western Europe (all P<0.05). Increased odds of not receiving any analgesia during delivery were demonstrated among parturients from North Africa, Sub-Saharan Africa, the Far East, North America, Eastern Europe, and India compared with western Europe (all P<0.05). CONCLUSIONS: Disparities exist in the use of intrapartum analgesia between migrant and western European populations in Ireland. Migrants from Africa were the least likely to use any analgesia. The reasons for this are speculative but could be influenced by expectations of care in the region of origin.

Epinephrine increases mortality after brief asphyxial cardiac arrest in an in vivo rat model.

Epinephrine may be detrimental in cardiac arrest. In this laboratory study we sought to characterize the effect of epinephrine and concomitant calcium channel blockade on postresuscitation myocardial performance after brief asphyxial cardiac arrest. Anesthesized rats were disconnected from mechanical ventilation, resulting in cardiac arrest. Resuscitation was attempted after 1 min with mechanical ventilation, oxygen, chest compressions, and IV medication. In experimental series 1 and 2, animals were allocated to 10 or 30 microg/kg epinephrine or 0.9% saline. In series 3, animals received 30 microg/kg of epinephrine and were randomized to 0.1 mg/kg of verapamil or to 0.9% saline. In series 1 and 3, left ventricular function was assessed using transthoracic echocardiography. In series 2, left atrial pressure was measured. Epinephrine was associated with increased mortality (0/8 [0%] in controls, 4/12 [33.3%] in 10 microg/kg animals, and 16/22 [72.8%] in 30 microg/kg animals; P < 0.05), hypertension (P < 0.001), tachycardia (P = 0.004), early transient left atrial hypertension, and dose-related reduction in left ventricular end diastolic diameter (P < 0.05). Verapamil prevented mortality associated with large-dose epinephrine (0% versus 100%) and attenuated early diastolic dysfunction and postresuscitation hypertension (P = 0.001) without systolic dysfunction. Epinephrine appears to be harmful in the setting of brief cardiac arrest after asphyxia.

The effect of global hypoxia on myocardial function after successful cardiopulmonary resuscitation in a laboratory model.

Most laboratory studies of cardiac arrest use models of ventricular fibrillation, but in the emergency room, operating room or intensive care unit, cardiac arrest frequently results from asphyxia. We sought to investigate the effect of different durations of asystole secondary to asphyxia on myocardial function after resuscitation. In a laboratory based experimental series, anaesthetized rats received either 4 or 8 min of asphyxial cardiac arrest, and following standardized resuscitation, serial transthoracic echocardiography was performed. Severe depression of left ventricular fractional shortening occurred in both groups with partial recovery only in the 4-min arrest group, while left ventricular end-diastolic diameter was increased in the 4-min group. The pH, HCO3(-) and SBE were reduced in both groups after resuscitation, but the degree of acidosis was greater in the 8-min group. In this model, transthoracic echocardiography demonstrated both systolic and diastolic impairment following asphyxial cardiac arrest, and a clear dose-effect relationship between duration of asphyxia and degree of impairment. A shorter duration of asphyxia was associated with a lesser increase in left ventricular end-diastolic dimension, compared with more protracted asphyxia; the shorter arrest was associated with better recovery of contractile function and acidosis. Increased duration of asphyxia causes increased systolic and diastolic dysfunction. These findings may have significant implications for resuscitative therapeutics. ECHO assessment may permit specific targeting of therapy directed towards systolic or diastolic function during CPR.

Airway management in the lateral position: a randomized controlled trial.

UNLABELLED: It may be required to ensure patency of the airway in the lateral position in certain circumstances. We performed a prospective randomized clinical trial investigating the effects of left lateral patient positioning on airway anatomy and subsequent airway management. Laryngoscopic airway examination was performed in anesthetized patients, in the supine and left lateral positions, and in the presence and absence of cricoid pressure. Patients were randomized to airway management via an endotracheal tube or laryngeal mask airway (LMA). The left lateral position resulted in a deterioration of laryngoscopic view in 35% of patients and improvement in none. In the lateral position, failure of airway management occurred in more patients with the endotracheal tube versus LMA (8 of 39 versus 1 of 30; P = 0.03), and the mean time to successful completion of airway management was longer with tracheal intubation compared with the LMA (39 +/- 19 s versus 26 +/- 12 s; P = 0.002). LMA use results in more reliable airway control compared to tracheal intubation in the lateral position. The LMA should be considered as the primary airway device when instituting airway management in this position. IMPLICATIONS: Inadequate airway management may be fatal. There are recommendations for airway difficulties, but the evidence favoring any specific strategy is limited. This study suggests that, in the lateral position, a laryngeal mask airway more rapidly and reliably establishes airway control than attempts at endotracheal intubation. It further suggests that placing a patient with an inadequate airway into the lateral position will hinder, not help, airway management.

Atelectasis causes vascular leak and lethal right ventricular failure in uninjured rat lungs.

During mechanical ventilation, lung recruitment attenuates injury caused by high VT, improves oxygenation, and may optimize pulmonary vascular resistance (PVR). We hypothesized that ventilation without recruitment would induce injury in otherwise healthy lungs. Anesthetized rats were ventilated with conventional mechanical ventilation (VT 8 ml/kg; respiratory frequency 40 per minute) and 21% inspired oxygen, with or without a recruitment strategy consisting of recruitment maneuvers plus positive end-expiratory pressure, in the presence or absence of a laparotomy. Additional experiments examined the impact of atelectasis on right ventricular function using echocardiography, as well as functional residual capacity and PVR. Lack of recruitment resulted in reduced overall survival (59% nonrecruited vs. 100% recruited, p < 0.05), increased microvascular leak, greater impairment of oxygenation and lung compliance, increased PVR, and elevated plasma lactate. Echocardiography demonstrated that right ventricular dysfunction occurred in the absence of recruitment. Finally, samples from nonrecruited lungs demonstrated ultrastructural evidence of microvascular endothelial disruption. Although such effects clearly do not occur with comparable magnitude in the clinical context, the current data suggest novel mechanisms (microvascular leak, right ventricular dysfunction) whereby derecruitment may contribute to development of lung injury and adverse systemic outcome.

European reference method for the in vivo determination of metabolisable energy with adult cockerels: reproducibility, effect of food intake and comparison with individual laboratory methods.

1. A common reference procedure adopted by several European laboratories to determine apparent metabolisable energy corrected to zero-nitrogen balance (AMEn) is described. 2. Reproducibility has been estimated by comparing results from 4 diets measured in 7 laboratories. The standard deviations between laboratories of dry matter, gross energy, Kjeldahl nitrogen and AMEn were respectively, on average, 11.29 g/kg, 0.242 MJ/kg, 1.56 g/kg and 0.380 MJ/kg dry matter; the corresponding coefficients of variation between laboratories were 1.27, 1.29, 4.39 and 2.92%. 3. Effect of food intake was tested by comparing AMEn from birds fed either 0.90 or 0.45 of ad libitum: the amount of food intake had a negligible effect on AMEn values. Endogenous energy losses corrected (EELn) or not (EEL) to zero nitrogen balance were estimated either by regression between excreted energy and ingested energy or in fasted and glucose-fed cockerels. EELn estimated by regression was, on average, 8.7 kJ/bird/d.; it was independent of diet composition. EEL and EELn determined in fasted or glucose-fed birds were higher than those determined by regression. 4. AMEn values measured by individual laboratory procedures were very close to those obtained by the reference method, except from laboratories using a tube feeding procedure, where deviations were probably a consequence of overestimated EEL.

European reference method of in vivo determination of metabolisable energy in poultry: reproducibility, effect of age, comparison with predicted values.

1. Apparent metabolisable energy corrected to zero-nitrogen retention (AMEn) was measured using the European reference procedure in 9 European laboratories. Seven pelleted diets were evaluated. AMEn was measured with adult cockerels and young birds. 2. Between-laboratory standard deviations were for dry matter (DM) 12.5 g/kg, gross energy 0.085 MJ/kg DM, Kjeldahl nitrogen 0.768 g/kg DM, AMEn (adults) 0.256 MJ/kg DM, and AMEn (young) 0.337 MJ/kg DM. Corresponding coefficients of variation between laboratories were 1.42, 0.45, 2.15, 1.88 and 2.60% respectively. 3. AMEn values of experimental diets were always significantly lower when measured with young birds. This effect was more pronounced when diets contained added fat. 4. Tallow or soyabean oil were incorporated into two basal diets at 40 g/kg inclusion rate. No significant differences were observed between AMEn values of either diet with adults or young birds, suggesting that AMEn energy values of these fats are indistinguishable at this inclusion rate. 5. Similar AMEn values were obtained in young birds by estimating nitrogen accretion, either by the difference between intake and excreta nitrogen or by measuring body weight gain. Determined AMEn values were very similar to those predicted using three different regression equations.

A methodological study of the relationship between the metabolizable energy values of two meat meals and their level of inclusion in the diet.

The nitrogen-corrected apparent (AMEn) and true (TMEn) metabolizable energy values of a low-fat and a high-fat meat meal (MM) were studied. Adult roosters were fed ad libitum on a basal diet or a mixture of the basal diet and one of the two MM. At up to 60% incorporation, MM were introduced at the expense of corn in the basal diet. Dietary inclusion was at 5, 10, 20, 40, and 60%; birds were also force-fed pure MM. The ME of MM decreased as MM content in the diet increased. Highest AMEn were observed when the MM was 5% of the diet (3356 and 1715 kcal/kg for the high- and low-fat MM, respectively); this may have been attributable to synergism of MM and basal diet fatty acids. The lower ME observed with higher MM could result from interactions between calcium and one or both fatty acids and proteins. It is concluded that ME of MM should be measured in diets containing low practical MM. Artificially high experimental levels of 50 or 100% may lead to underestimation of the energy of MM.

Evaluation of the effect of anticoccidial drugs on size of parasite population and its development in litters.

Evaluation of the number of oocysts present in liters and of their rate of sporulation is relatively easy in floor pens. We have observed that contamination varies considerably according to the anticoccidial drug present in feed. Despite a difference in effect on parasitic development, some identical performances were noted in all groups treated. Among the anticoccidial drugs studied, Monensin is the one which least reduces contamination of environment; Halofuginone is the one which reduces contamination the most.

Evaluation of the clastogenic action of benzene by oral administration with 2 cytogenetic techniques in mouse and Chinese hamster.

In previous studies, we found, using the micronucleus test, that the adult male mouse is about twice as sensitive as the female to the clastogenic action of orally administered benzene (Siou and Conan, 1978). For new-born mice suckling mothers receiving benzene orally (Siou and Conan, 1979), or for three-week-old mice receiving benzene orally (Siou and Conan, 1980), there was no significant difference in sensitivity between females and castrated males; castrated males treated with testosterone regained their original sensitivity. The objectives of the experiments described here were to confirm these findings by metaphase chromosome analysis of bone-marrow cells from mice and Chinese hamsters. Metaphase chromosome studies and micronucleus counts were performed on each animal to investigate the relationship between the 2 techniques.

Evaluation of the efficacy of salinomycin in the control of coccidiosis in chicks.

Salinomycin (Coxistac) was tested for efficacy in broilers reared in floor pens at 60 and 80 ppm fed continuously from 1 to 56 days of age. One trial was conducted. Comparisons were made with unmedicated, infected and medicated, noninfected treatments (controls) in addition to infected treatments given either monensin at 100 ppm or halofuginone at 3 ppm continuously (days 1 to 56) in the feed. Coccidia exposure was obtained by infection via the feed. Salinomycin was highly efficacious at 60 ppm based upon improved performance, lesion score, hematocrit, and serum optical density compared with the unmedicated, infected group. Statistical analysis of main effects on weight gain, feed conversion ratio, hematocrit value, and serum optical density showed no significant differences between salinomycin, monensin, or halofuginone. The weight gain of birds given salinomycin at 80 ppm was depressed significantly (P less than .01) at 56 days as a result of decreased feed consumption.