Cardiovascular and hematological responses to a dry dynamic apnea in breath hold divers.

The mammalian dive reflex, characterized by bradycardia and peripheral vasoconstriction, occurs in all mammals, including humans, in response to apnea. However, the dive reflex to a single, maximal, dry, dynamic apnea (DYN) and how it compares to a time-matched exercise control trial (EX) or dry static apnea (SA) has not been studied. We examined the hypotheses that, compared with EX and SA, the magnitude of the 1) cardiovascular response and 2) hematological response to DYN would be greater. Cardiovascular parameters [heart rate (HR), systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure] were continuously collected in 23 (F = 6 females) moderate and elite freedivers, first during a maximal DYN, then during a time-matched SA and EX on a swimming ergometer in randomized order. Venous blood draws were made before and following each trial. The change in calculated oxygen saturation (DYN: -17 ± 13%, EX: -2 ± 1%, ΔSA: -2 ± 1%; P < 0.05, all comparisons) was greater during DYN compared with EX and SA. During DYN, ΔSBP (DYN: 104 ± 31 mmHg; EX: 38 ± 23 mmHg; and SA: 20 ± 11 mmHg), ΔDBP (DYN: 45 ± 12 mmHg; EX: 14 ± 10 mmHg; and SA: 15 ± 8 mmHg), and ΔMAP (DYN: 65 ± 17 mmHg; EX: 22 ± 13 mmHg; and SA: 16 ± 9 mmHg) were increased compared with EX and SA, while ΔHR was greater during EX (DYN: -24 ± 23 beats/min; EX: 33 ± 13 beats/min; and SA: -1 ± 10 beats/min) than either DYN or SA (P < 0.0001, all comparisons). Females had a greater pressor response to EX (ΔSBP: 59 ± 30 mmHg; ΔDBP: 24 ± 14 mmHg; and ΔMAP: 35 ± 8 mmHg) than males (ΔSBP: 31 ± 15 mmHg; ΔDBP: 11 ± 6 mmHg; and ΔMAP: 18 ± 8 mmHg; P < 0.01, all comparisons). Together, these data indicate that DYN elicits a distinct, exaggerated cardiovascular response compared with EX or SA alone.NEW & NOTEWORTHY This study performed a dry dynamic apnea with sport-specific equipment to closely mimic the physiological demands of competition diving. We found the cardiovascular and hematological responses to dynamic apnea were more robust compared with time-matched exercise and dry static apnea control trials.

Selected and shared hematological responses to apnea in elite human free divers and northern elephant seals (Mirounga angustirostris).

Despite elite human free divers achieving incredible feats in competitive free diving, there has yet to be a study that compares consummate divers, (i.e. northern elephant seals) to highly conditioned free divers (i.e., elite competitive free-diving humans). Herein, we compare these two diving models and suggest that hematological traits detected in seals reflect species-specific specializations, while hematological traits shared between the two species are fundamental mammalian characteristics. Arterial blood samples were analyzed in elite human free divers (n = 14) during a single, maximal volitional apnea and in juvenile northern elephant seals (n = 3) during rest-associated apnea. Humans and elephant seals had comparable apnea durations (∼6.5 min) and end-apneic arterial Po2 [humans: 40.4 ± 3.0 mmHg (means ± SE); seals: 27.1 ± 5.9 mmHg; P = 0.2]. Despite similar increases in arterial Pco2 (humans: 33 ± 5%; seals: 16.3 ± 5%; P = 0.2), only humans experienced reductions in pH from baseline (humans: 7.45 ± 0.01; seals: 7.39 ± 0.02) to end apnea (humans: 7.37 ± 0.01; seals: 7.38 ± 0.02; P < 0.0001). Hemoglobin P50 was greater in humans compared to elephant seals (29.9 ± 1.5 and 28.7 ± 0.6 mmHg, respectively; P = 0.046). Elephant seals overall had higher carboxyhemoglobin (COHb) levels (5.9 ± 2.6%) compared to humans (0.8 ± 1.2%; P < 0.0001); however, following apnea, COHb was reduced in seals (baseline: 6.1 ± 0.3%; end apnea: 5.6 ± 0.3%) and was slightly elevated in humans (baseline: 0.7 ± 0.1%; end apnea: 0.9 ± 0.1%; P < 0.0002, both comparisons). Our data indicate that during static apnea, seals have reduced hemoglobin P50, greater pH buffering, and increased COHb levels. The differences in hemoglobin P50 are likely due to the differences in the physiological environment between the two species during apnea, whereas enhanced pH buffering and higher COHb may represent traits selected for in elephant seals.NEW & NOTEWORTHY This study uses similar methods and protocols in elite human free divers and northern elephant seals. Using highly conditioned divers (elite free-diving humans) and highly adapted divers (northern elephant seals), we explored which hematological traits are fundamentally mammalian and which may have been selected for. We found differences in P50, which may be due to different physiological environments between species, while elevated pH buffering and carbon monoxide levels might have been selected for in seals.

Effect of exercise intensity and apnea on splenic contraction and hemoglobin increase in well-trained cross-country skiers.

The human spleen acts as a reservoir for red blood cells, which is mobilized into the systemic circulation during various conditions such as hypoxia and physical exertion. Cross-country (XC) skiers, renowned for their exceptional aerobic capacity, are regularly exposed to high-intensity exercise and local oxygen deficits. We investigated a putative dose-dependent relationship between splenic contraction and concomitant hemoglobin concentration ([Hb]) elevation across four exercise intensities in well-trained XC skiers. Fourteen male XC skiers voluntarily participated in a 2-day protocol, encompassing a serial apnea test and a V ˙ O2max test (day 1), followed by three submaximal exercise intensities on a roller skiing treadmill corresponding to 55, 70, and 85% of V ˙ O2max (day 2). Spleen volume was measured via ultrasonic imaging, and venous blood samples were used to determine [Hb] levels. Baseline spleen volume was similar (266(35) mL) for all conditions (NS). Notably, all conditions induced significant splenic contractions and transient [Hb] elevations. The V ˙ O2max test exhibited the most pronounced splenic contraction (35.8%, p < 0.001) and a [Hb] increase of 8.1%, while the 85% exercise intensity led to 27.1% contraction and the greatest [Hb] increase (8.3%, < 0.001) compared to baseline. The apnea test induced relatively smaller responses (splenic contraction: 20.4%, [Hb] = 3.3%, p < 0.001), akin to the response observed at the 70% exercise intensity (splenic contraction = 23%, [Hb] = 6.4%, p < 0,001) and 55% (splenic contraction = 20.0%, [Hb] = 4.8%, p < 0.001). This study shows a discernible dose-dependent relationship between splenic contraction and [Hb] increase with levels of exercise, effectively distinguishing between submaximal and maximal exercise intensity.

Acute effects of apnea bouts on hemoglobin concentration and hematocrit: a systematic review and meta-analysis.

Objective: This study aimed to systematically analyze the existing literature and conduct a meta-analysis on the acute effects of apnea on the hematological response by assessing changes in hemoglobin (Hb) concentration and hematocrit (Hct) values. Methods: Searches in Pubmed, The Cochrane Library, and Web of Science were carried out for studies in which the main intervention was voluntary hypoventilation, and Hb and Hct values were measured. Risk of bias and quality assessments were performed. Results: Nine studies with data from 160 participants were included, involving both subjects experienced in breath-hold sports and physically active subjects unrelated to breath-holding activities. The GRADE scale showed a "high" confidence for Hb concentration, with a mean absolute effect of 0.57 g/dL over control interventions. "Moderate" confidence appeared for Hct, where the mean absolute effect was 2.45% higher over control interventions. Hb concentration increased to a greater extent in the apnea group compared to the control group (MD = 0.57 g/dL [95% CI 0.28, 0.86], Z = 3.81, p = 0.0001) as occurred with Hct (MD = 2.45% [95% CI 0.98, 3.93], Z = 3.26, p = 0.001). Conclusions: Apnea bouts lead to a significant increase in the concentration of Hb and Hct with a high and moderate quality of evidence, respectively. Further trials on apnea and its application to different settings are needed.

Carbon Dioxide Changes during High-flow Nasal Oxygenation in Apneic Patients: A Single-center Randomized Controlled Noninferiority Trial.

BACKGROUND: Anesthesia studies using high-flow, humidified, heated oxygen delivered via nasal cannulas at flow rates of more than 50 l · min-1 postulated a ventilatory effect because carbon dioxide increased at lower levels as reported earlier. This study investigated the increase of arterial partial pressure of carbon dioxide between different flow rates of 100% oxygen in elective anesthetized and paralyzed surgical adults before intubation. METHODS: After preoxygenation and standardized anesthesia induction with nondepolarizing neuromuscular blockade, all patients received 100% oxygen (via high-flow nasal oxygenation system or circuit of the anesthesia machine), and continuous jaw thrust/laryngoscopy was applied throughout the 15-min period. In this single-center noninferiority trial, 25 patients each, were randomized to five groups: (1) minimal flow: 0.25 l · min-1, endotracheal tube; (2) low flow: 2 l · min-1, continuous jaw thrust; (3) medium flow: 10 l · min-1, continuous jaw thrust; (4) high flow: 70 l · min-1, continuous jaw thrust; and (5) control: 70 l · min-1, continuous laryngoscopy. Immediately after anesthesia induction, the 15-min apnea period started with oxygen delivered according to the randomized flow rate. Serial arterial blood gas analyses were drawn every 2 min. The study was terminated if either oxygen saturation measured by pulse oximetry was less than 92%, transcutaneous carbon dioxide was greater than 100 mmHg, pH was less than 7.1, potassium level was greater than 6 mmol · l-1, or apnea time was 15 min. The primary outcome was the linear rate of mean increase of arterial carbon dioxide during the 15-min apnea period computed from linear regressions. RESULTS: In total, 125 patients completed the study. Noninferiority with a predefined noninferiority margin of 0.3 mmHg · min-1 could be declared for all treatments with the following mean and 95% CI for the mean differences in the linear rate of arterial partial pressure of carbon dioxide with associated P values regarding noninferiority: high flow versus control, -0.0 mmHg · min-1 (-0.3, 0.3 mmHg · min-1, P = 0.030); medium flow versus control, -0.1 mmHg · min-1 (-0.4, 0.2 mmHg · min-1, P = 0.002); low flow versus control, -0.1 mmHg · min-1 (-0.4, 0.2 mmHg · min-1, P = 0.003); and minimal flow versus control, -0.1 mmHg · min-1 (-0.4, 0.2 mmHg · min-1, P = 0.004). CONCLUSIONS: Widely differing flow rates of humidified 100% oxygen during apnea resulted in comparable increases of arterial partial pressure of carbon dioxide, which does not support an additional ventilatory effect of high-flow nasal oxygenation.

The Effect of High-Flow Nasal Oxygen on Carbon Dioxide Accumulation in Apneic or Spontaneously Breathing Adults During Airway Surgery: A Randomized-Controlled Trial.

BACKGROUND: High-flow nasal oxygen (HFNO) is an emerging technology that has generated interest in tubeless anesthesia for airway surgery. HFNO has been shown to maintain oxygenation and CO2 clearance in spontaneously breathing patients and is an effective approach to apneic oxygenation. Although it has been suggested that HFNO can enhance CO2 clearance during apnea, this has not been established. The true extent of CO2 accumulation and resulting acidosis using HFNO during prolonged tubeless anesthesia remains undefined. METHODS: In a single-center trial, we randomly assigned 20 adults undergoing microlaryngoscopy to apnea or spontaneous ventilation (SV) using HFNO during 30 minutes of tubeless anesthesia. Serial arterial blood gas analysis was performed during preoxygenation and general anesthesia. The primary outcome was the partial pressure of CO2 (Paco2) after 30 minutes of general anesthesia, with each group compared using a Student t test. RESULTS: Nineteen patients completed the study protocol (9 in the SV group and 10 in the apnea group). The mean (standard deviation [SD]) Paco2 was 89.0 mm Hg (16.5 mm Hg) in the apnea group and 55.2 mm Hg (7.2 mm Hg) in the SV group (difference in means, 33.8; 95% confidence interval [CI], 20.6-47.0) after 30 minutes of general anesthesia (P < .001). The average rate of Paco2 rise during 30 minutes of general anesthesia was 1.8 mm Hg/min (SD = 0.5 mm Hg/min) in the apnea group and 0.8 mm Hg/min (SD = 0.3 mm Hg/min) in the SV group. The mean (SD) pH was 7.11 (0.04) in the apnea group and 7.29 (0.06) in the SV group (P < .001) at 30 minutes. Five (55%) of the apneic patients had a pH <7.10, of which the lowest measurement was 7.057. No significant difference in partial pressure of arterial O2 (Pao2) was observed after 30 minutes of general anesthesia. CONCLUSIONS: CO2 accumulation during apnea was more than double that of SV after 30 minutes of tubeless anesthesia using HFNO. The use of robust measurement confirms that apnea with HFNO is limited by CO2 accumulation and the concomitant severe respiratory acidosis, in contrast to SV. This extends previous knowledge and has implications for the safe application of HFNO during prolonged procedures.

Oxygen Reserve Index: Utility as an Early Warning for Desaturation in High-Risk Surgical Patients.

BACKGROUND: Perioperative pulse oximetry hemoglobin saturation (Spo2) measurement is associated with fewer desaturation and hypoxia episodes. However, the sigmoidal nature of oxygen-hemoglobin dissociation limits the accuracy of estimation of the partial pressure of oxygen (Pao2) >80 mm Hg and correspondingly limits the ability to identify when Pao2 >80 mm Hg but falling. We hypothesized that a proxy measurement for oxygen saturation (Oxygen Reserve Index [ORI]) derived from multiwavelength pulse oximetry may allow additional warning time before critical desaturation or hypoxia. To test our hypothesis, we used a Masimo multiwavelength pulse oximeter to compare ORI and Spo2 warning times during apnea in high-risk surgical patients undergoing cardiac surgery. METHODS: This institutional review board-approved prospective study (NCT03021473) enrolled American Society of Anesthesiologists physical status III or IV patients scheduled for elective surgery with planned preinduction arterial catheter placement. In addition to standard monitors, an ORI sensor was placed and patients were monitored with a pulse oximeter displaying the ORI, a nondimensional parameter that ranges from 0 to 1. Patients were then preoxygenated until ORI plateaued. Following induction of anesthesia, mask ventilation with 100% oxygen was performed until neuromuscular blockade was established. Endotracheal intubation was accomplished using videolaryngoscopy to confirm placement. The endotracheal tube was not connected to the breathing circuit, and patients were allowed to be apneic. Ventilation was resumed when Spo2 reached 94%. We defined ORI warning time as the time from when the ORI alarm registered (based on the absolute value and the rate of change) until the Spo2 decreased to 94%. We defined the Spo2 warning time as the time for Spo2 to decrease from 97% to 94%. The added warning time provided by ORI was defined as the difference between ORI warning time and Spo2 warning time. RESULTS: Forty subjects were enrolled. Complete data for analysis were available from 37 patients. The ORI alarm registered before Spo2 decreasing to 97% in all patients. Median (interquartile range [IQR]) ORI warning time was 80.4 seconds (59.7-105.9 seconds). Median (IQR) Spo2 warning time was 29.0 seconds (20.5-41.0 seconds). The added warning time provided by ORI was 48.4 seconds (95% confidence interval [CI], 40.4-62.0 seconds; P < .0001). CONCLUSIONS: In adult high-risk surgical patients, ORI provided clinically relevant added warning time of impending desaturation compared to Spo2. This additional time may allow modification of airway management, earlier calls for help, or assistance from other providers. The potential patient safety impact of such monitoring requires further study.

Changes in PUFA and eicosanoid metabolism during/after apnea diving: a prospective single-center study.

Background: The popularity of apneic diving is continually growing. As apnea diving substantially burdens the cardiovascular system, special focus is warranted. Regarding inflammation processes and associated inflammatory-related diseases (e.g., cardiovascular diseases), eicosanoids play an important role. This study aims to investigate polyunsaturated fatty acids (PUFAs) and eicosanoids in voluntary apnea divers, and so to further improve understanding of pathophysiological processes focusing on proinflammatory effects of temporarily hypercapnic hypoxia.. Methods: The concentration of PUFAs and eicosanoids were investigated in EDTA plasma in apnea divers (n=10) before and immediately after apnea, 0.5 hour and four hours later, applying liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Mean age was 41±10 years, and divers performed a mean breath-hold time of 317±111 seconds. PUFAs, eicosanoids and related lipids could be classified in four different kinetical reaction groups following apnea. The first group (e.g., Ω-6 and Ω-3-PUFAs) showed an immediate concentration increase followed by a decrease below baseline four hours after apnea. The second group (e.g., thromboxane B2) showed a slower increase, with its maximum concentration 0.5 hour post-apnea followed by a decrease four hours post-apnea. Group 3 (9- and 13-hydroxyoctadecadienoic acid) is characterized by two concentration increase peaks directly after apnea and four hours afterward compared to baseline. Group 4 (e.g., prostaglandin D2) shows no clear response. Conclusion: Changes in the PUFA metabolism after even a single apnea revealed different kinetics of pro- and anti-inflammatory regulations and changes for oxidative stress levels. Due to the importance of these mediators, apnea diving should be evaluated carefully and be performed only with great caution against the background of cardiovascular diseases and inflammation processes.

Influence of prevention of caffeine citrate on cytokine profile and bronchopulmonary dysplasia in preterm infants with apnea.

BACKGROUND: This study aims to investigate the preventive effects of caffeine citrate on cytokine profile and bronchopulmonary dysplasia (BPD) in preterm infants with apnea. METHODS: Preterm infants with apnea who were born at less than 32 weeks of gestational age and birth weight ≤1500 g were randomly divided into caffeine citrate prevention group and caffeine citrate treatment group. Preterm infants in caffeine citrate prevention group who were at risk of developing recurrent apnea were given to caffeine citrate within 8 h after birth. Those in caffeine citrate treatment group experienced apnea after birth were given to caffeine citrate for treatment. Preterm infants in both groups were treated with the same respiratory management and other conventional therapy. After drug discontinuation, levels of cytokine profile, and incidence of BPD were compared between two groups. RESULTS: A total of 56 preterm infants were enrolled. Differences in gestational age (P=0.11) and birth weight (P=0.251) were not statistically significant. Differences in application time of caffeine citrate (P=0.356), hour of ventilator use (P=0.152), length of stay (P=0.416) and BPD morbidity (P=1.00) between two groups were not statistically significant. At birth, there were no statistically significant in levels of IL-6 (P=0.063) and IL-8 (P=0.125) between two groups. After conventional therapy, levels of IL-6 (P=0.001) and IL-8 (P=0.001) significantly decreased in caffeine citrate prevention group compared with those in caffeine citrate treatment group. CONCLUSIONS: Prevention usage of caffeine citrate in preterm infants with apnea could reduce the level of cytokine profile and the incidence of BPD.

Competitive apnea and its effect on the human brain: focus on the redox regulation of blood-brain barrier permeability and neuronal-parenchymal integrity.

Static apnea provides a unique model that combines transient hypertension, hypercapnia, and severe hypoxemia. With apnea durations exceeding 5 min, the purpose of the present study was to determine how that affects cerebral free-radical formation and the corresponding implications for brain structure and function. Measurements were obtained before and following a maximal apnea in 14 divers with transcerebral exchange kinetics, measured as the product of global cerebral blood flow (duplex ultrasound) and radial arterial to internal jugular venous concentration differences ( a-vD). Apnea increased the systemic (arterial) and, to a greater extent, the regional (jugular venous) concentration of the ascorbate free radical, resulting in a shift from net cerebral uptake to output ( P < 0.05). Peroxidation (lipid hydroperoxides, LDL oxidation), NO bioactivity, and S100ß were correspondingly enhanced ( P < 0.05), the latter interpreted as minor and not a pathologic disruption of the blood-brain barrier. However, those changes were insufficient to cause neuronal-parenchymal damage confirmed by the lack of change in the a-vD of neuron-specific enolase and human myelin basic protein ( P > 0.05). Collectively, these observations suggest that increased cerebral oxidative stress following prolonged apnea in trained divers may reflect a functional physiologic response, rather than a purely maladaptive phenomenon.-Bain, A. R., Ainslie, P. N., Hoiland, R. L., Barak, O. F., Drvis, I., Stembridge, M., MacLeod, D. M., McEneny, J., Stacey, B. S., Tuaillon, E., Marchi, N., De Maudave, A. F., Dujic, Z., MacLeod, D. B., Bailey, D. M. Competitive apnea and its effect on the human brain: focus on the redox regulation of blood-brain barrier permeability and neuronal-parenchymal integrity.

High-Flow Nasal Oxygen Improves Safe Apnea Time in Morbidly Obese Patients Undergoing General Anesthesia: A Randomized Controlled Trial.

BACKGROUND: Morbidly obese patients undergoing general anesthesia are at risk of hypoxemia during anesthesia induction. High-flow nasal oxygenation use during anesthesia induction prolongs safe apnea time in nonobese surgical patients. The primary objective of our study was to compare safe apnea time, between patients given high-flow nasal oxygenation or conventional facemask oxygenation during anesthesia induction, in morbidly obese surgical patients. METHODS: Research ethics board approval was obtained. Elective surgical patients ≥18 years with body mass index ≥40 kg·m were included. Patients with severe comorbidity, gastric reflux disease, known difficult airway, or nasal obstruction were excluded. After obtaining informed consent patients were randomized. In the intervention (high-flow nasal oxygenation) group, preoxygenation was provided by 100% nasal oxygen for 3 minutes at 40 L·minute; in the control group, preoxygenation was delivered using a facemask with 100% oxygen, targeting end-tidal O2 >85%. Anesthesia was induced with propofol, remifentanil, and rocuronium. Bag-mask ventilation was not performed. At 2 minutes after rocuronium, videolaryngoscopy was performed. If the laryngoscopy grade was I or II, laryngoscope was left in place and the study was continued; if grade III or IV was observed, the patient was excluded from the study. During the apnea period, high-flow nasal oxygenation patients received nasal oxygen at 60 L·minute; control group patients received no supplemental oxygen. The primary outcome, safe apnea time, was reached when oxygen saturation measured by pulse oximetry (SpO2) fell to 95% or maximum 6 minutes of apnea. The patient was then intubated. T tests and χ analyses were used to compare groups. P < .05 was considered significant. RESULTS: Forty patients completed the study. Baseline parameters were comparable between groups. Safe apnea time was significantly longer (261.4 ± 77.7 vs 185.5 ± 52.9 seconds; mean difference [95% CI], 75.9 [33.3-118.5]; P = .001) and the minimum peri-intubation SpO2 was higher (91.0 ± 3.5 vs 88.0 ± 4.8; mean difference [95% CI], 3.1 [0.4-5.7]; P = .026) in the high-flow nasal oxygenation group compared to the control group. CONCLUSIONS: High-flow nasal oxygenation, compared to conventional oxygenation, provided a longer safe apnea time by 76 seconds (40%) and higher minimum SpO2 in morbidly obese patients during anesthesia induction. High-flow oxygenation use should be considered in morbidly obese surgical patients.

Erythropoietic responses to a series of repeated maximal dynamic and static apnoeas in elite and non-breath-hold divers.

PURPOSE: Serum erythropoietin (EPO) concentration is increased following static apnoea-induced hypoxia. However, the acute erythropoietic responses to a series of dynamic apnoeas in non-divers (ND) or elite breath-hold divers (EBHD) are unknown. METHODS: Participants were stratified into EBHD (n = 8), ND (n = 10) and control (n = 8) groups. On two separate occasions, EBHD and ND performed a series of five maximal dynamic apnoeas (DYN) or two sets of five maximal static apnoeas (STA). Control performed a static eupnoeic (STE) protocol to control against any effects of water immersion and diurnal variation on EPO. Peripheral oxygen saturation (SpO2) levels were monitored up to 30 s post each maximal effort. Blood samples were collected at 30, 90, and 180 min after each protocol for EPO, haemoglobin and haematocrit concentrations. RESULTS: No between group differences were observed at baseline (p > 0.05). For EBHD and ND, mean end-apnoea SpO2 was lower in DYN (EBHD, 62 ± 10%, p = 0.024; ND, 85 ± 6%; p = 0.020) than STA (EBHD, 76 ± 7%; ND, 96 ± 1%) and control (98 ± 1%) protocols. EBHD attained lower end-apnoeic SpO2 during DYN and STA than ND (p < 0.001). Serum EPO increased from baseline following the DYN protocol in EBHD only (EBHD, p < 0.001; ND, p = 0.622). EBHD EPO increased from baseline (6.85 ± 0.9mlU/mL) by 60% at 30 min (10.82 ± 2.5mlU/mL, p = 0.017) and 63% at 180 min (10.87 ± 2.1mlU/mL, p = 0.024). Serum EPO did not change after the STA (EBHD, p = 0.534; ND, p = 0.850) and STE (p = 0.056) protocols. There was a significant negative correlation (r = - 0.49, p = 0.003) between end-apnoeic SpO2 and peak post-apnoeic serum EPO concentrations. CONCLUSIONS: The novel findings demonstrate that circulating EPO is only increased after DYN in EBHD. This may relate to the greater hypoxemia achieved by EBHD during the DYN.

Cardiovascular magnetic resonance assessment of acute cardiovascular effects of voluntary apnoea in elite divers.

BACKGROUND: Prolonged breath holding results in hypoxemia and hypercapnia. Compensatory mechanisms help maintain adequate oxygen supply to hypoxia sensitive organs, but burden the cardiovascular system. The aim was to investigate human compensatory mechanisms and their effects on the cardiovascular system with regard to cardiac function and morphology, blood flow redistribution, serum biomarkers of the adrenergic system and myocardial injury markers following prolonged apnoea. METHODS: Seventeen elite apnoea divers performed maximal breath-hold during cardiovascular magnetic resonance imaging (CMR). Two breath-hold sessions were performed to assess (1) cardiac function, myocardial tissue properties and (2) blood flow. In between CMR sessions, a head MRI was performed for the assessment of signs of silent brain ischemia. Urine and blood samples were analysed prior to and up to 4 h after the first breath-hold. RESULTS: Mean breath-hold time was 297 ± 52 s. Left ventricular (LV) end-systolic, end-diastolic, and stroke volume increased significantly (p < 0.05). Peripheral oxygen saturation, LV ejection fraction, LV fractional shortening, and heart rate decreased significantly (p < 0.05). Blood distribution was diverted to cerebral regions with no significant changes in the descending aorta. Catecholamine levels, high-sensitivity cardiac troponin, and NT-pro-BNP levels increased significantly, but did not reach pathological levels. CONCLUSION: Compensatory effects of prolonged apnoea substantially burden the cardiovascular system. CMR tissue characterisation did not reveal acute myocardial injury, indicating that the resulting cardiovascular stress does not exceed compensatory physiological limits in healthy subjects. However, these compensatory mechanisms could overly tax those limits in subjects with pre-existing cardiac disease. For divers interested in competetive apnoea diving, a comprehensive medical exam with a special focus on the cardiovascular system may be warranted. TRIAL REGISTRATION: This prospective single-centre study was approved by the institutional ethics committee review board. It was retrospectively registered under ClinicalTrials.gov (Trial registration: NCT02280226 . Registered 29 October 2014).

A Retrospective Study to Compare the Use of the Mean Apnea-Hypopnea Duration and the Apnea-Hypopnea Index with Blood Oxygenation and Sleep Patterns in Patients with Obstructive Sleep Apnea Diagnosed by Polysomnography.

BACKGROUND The apnea-hypopnea index (AHI) and the mean apnea-hypopnea duration (MAD) are used to measure the severity of the symptoms of obstructive sleep apnea (OSA). The aim of this study was to compare the use of the MAD with the AHI as indicators of clinical and demographic parameters, blood oxygenation, and sleep parameters in patients diagnosed with OSA by polysomnography (PSG). MATERIAL AND METHODS A retrospective study included 511 patients with OSA diagnosed by PSG and who had the AHI and the MAD measured according to the guidelines from the American Academy of Sleep Medicine (AASM). The patients were divided into two groups: patients with a short MAD and with a long MAD, according to median duration, and using the inter-quartile range (IQR), as the data were not normally distributed. Clinical and demographic parameters were recorded. Pulse oximetry was used to measure blood oxygen saturation during sleep, sleep structure was recorded, and the Epworth Sleepiness Scale (ESS) questionnaire was used to measure daytime sleepiness. RESULTS In all 511 patients with OSA, the MAD was significantly, but weakly, correlated with the AHI (r=0.17, P<0.01), but showed no significant associations with patient age (r=0.08, P=0.06), body weight (r=0.014, P=0.75), and height (r=0.06, P=0.16). Patients with a long MAD or severe OSA (n=260) had significantly worse blood oxygen levels and sleep parameters. CONCLUSIONS For patients with severe OSA, this study showed that the MAD was a useful indicator of blood oxygenation and sleep parameters.

Emergency ventilation with the Ventrain® through an airway exchange catheter in a porcine model of complete upper airway obstruction.

PURPOSE: During difficult airway management, oxygen insufflation through airway-exchange and intubating catheters (AEC/IC) can lead to life-threatening hyperinflation. Ventrain® was originally designed to facilitate emergency ventilation using active expiration through short, small-bore cannulas. Herein, we studied its efficacy (oxygenation and ventilation) and safety (avoidance of hyperinflation) in a long, small-bore AEC. METHODS: In six anesthetized pigs, the upper airway was obstructed, except for a 100 cm long, 3 mm internal diameter AEC. After apneic desaturation to a peripheral oxygen saturation (SpO2) of < 70%, ventilation through the AEC was started with Ventrain at an oxygen flow of 15 L·min-1, a frequency of 30 breaths·min-1, and an inspiration/expiration ratio of approximately 1:1. It was continued for ten minutes. RESULTS: Within one minute, severe hypoxia was reversed from a median [interquartile range] arterial saturation (SaO2) of 48 [34-56] % before initiation of Ventrain ventilation to 100 [99-100] % afterward (median difference 54%; 95% confidence interval [CI] 44 to 67; P = 0.028). In addition, hypercarbia was reversed from PaCO2 of 59 [53-61] mmHg to 40 [38-42] mmHg (median difference of -18 mmHg; 95% CI -21 to -15; P = 0.028). After ten minutes of Ventrain use, peak inspiratory and end-expiratory pressures were lower than during baseline pressure-controlled ventilation (8 [7-9] mmHg vs 12 [10-14] mmHg and -2 [-3 to +1] mmHg vs 4 [2 to 4] mmHg, respectively; P = 0.027 for both). No hemodynamic deterioration occurred. CONCLUSION: Ventrain provides rapid reoxygenation and effective ventilation through a small-bore AEC in pigs with an obstructed airway. In clinical emergency situations of obstructed airways, this device may be able to overcome problems of unintentional hyperinflation and high intrapulmonary pressures when ventilating through long, small-bore catheters and could therefore minimize the risks of barotrauma and hemodynamic instability.

Influence of Apnea-induced Hypoxia on Catecholamine Release and Cardiovascular Dynamics.

Prolonged breath-hold causes complex compensatory mechanisms such as increase in blood pressure, redistribution of blood flow, and bradycardia. We tested whether apnea induces an elevation of catecholamine-concentrations in well-trained apneic divers.11 apneic divers performed maximal dry apnea in a horizontal position. Parameters measured during apnea included blood pressure, ECG, and central, in addition to peripheral hemoglobin oxygenation. Peripheral arterial hemoglobin oxygenation was detected by pulse oximetry, whereas peripheral (abdominal) and central (cerebral) tissue oxygenation was measured by Near Infrared Spectroscopy (NIRS). Exhaled O2 and CO2, plasma norepinephrine and epinephrine concentrations were measured before and after apnea.Averaged apnea time was 247±76 s. Systolic blood pressure increased from 135±13 to 185±25 mmHg. End-expiratory CO2 increased from 29±4 mmHg to 49±6 mmHg. Norepinephrine increased from 623±307 to 1 826±984 pg ml-1 and epinephrine from 78±22 to 143±65 pg ml-1 during apnea. Heart rate reduction was inversely correlated with increased norepinephrine (correlation coefficient -0.844, p=0.001). Central (cerebral) O2 desaturation was time-delayed compared to peripheral O2 desaturation as measured by NIRSabdominal and SpO2.Increased norepinephrine caused by apnea may contribute to blood shift from peripheral tissues to the CNS and thus help to preserve cerebral tissue O2 saturation longer than that of peripheral tissue.

Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia.

KEY POINTS: The present study describes the cerebral oxidative and non-oxidative metabolism in man during a prolonged apnoea (ranging from 3 min 36 s to 7 min 26 s) that generates extremely low levels of blood oxygen and high levels of carbon dioxide. The cerebral oxidative metabolism, measured from the product of cerebral blood flow and the radial artery-jugular venous oxygen content difference, was reduced by ∼29% at the termination of apnoea, although there was no change in the non-oxidative metabolism. A subset study with mild and severe hypercapnic breathing at the same level of hypoxia suggests that hypercapnia can partly explain the cerebral metabolic reduction near the apnoea breakpoint. A hypercapnia-induced oxygen-conserving response may protect the brain against severe oxygen deprivation associated with prolonged apnoea. ABSTRACT: Prolonged apnoea in humans is reflected in progressive hypoxaemia and hypercapnia. In the present study, we explore the cerebral metabolic responses under extreme hypoxia and hypercapnia associated with prolonged apnoea. We hypothesized that the cerebral metabolic rate for oxygen (CMRO2 ) will be reduced near the termination of apnoea, attributed in part to the hypercapnia. Fourteen elite apnoea-divers performed a maximal apnoea (range 3 min 36 s to 7 min 26 s) under dry laboratory conditions. In a subset study with the same divers, the impact of hypercapnia on cerebral metabolism was determined using varying levels of hypercapnic breathing, against the background of similar hypoxia. In both studies, the CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-internal jugular venous oxygen content difference. Non-oxidative cerebral metabolism was calculated from the ratio of oxygen and carbohydrate (lactate and glucose) metabolism. The CMRO2  was reduced by ∼29% (P < 0.01, Cohen's d = 1.18) near the termination of apnoea compared to baseline, although non-oxidative metabolism remained unaltered. In the subset study, in similar backgrounds of hypoxia (arterial O2 tension: ∼38.4 mmHg), severe hypercapnia (arterial CO2 tension: ∼58.7 mmHg), but not mild-hypercapnia (arterial CO2 tension: ∼46.3 mmHg), depressed the CMRO2 (∼17%, P = 0.04, Cohen's d = 0.87). Similarly to the apnoea, there was no change in the non-oxidative metabolism. These data indicate that hypercapnia can partly explain the reduction in CMRO2 near the apnoea breakpoint. This hypercapnic-induced oxygen conservation may protect the brain against severe hypoxaemia associated with prolonged apnoea.

Mechanisms of modulation of cytokine release by human cord blood monocytes exposed to high concentrations of caffeine.

BACKGROUND: Serum caffeine concentrations >20 µg/ml (100 µmol/l) in infants treated for apnea of prematurity increases TNF-α and decreases IL-10, changes that perhaps are linked to comorbidities. We hypothesize that this proinflammatory cytokine profile may be linked to differential binding of caffeine to adenosine receptor subtypes (AR), inhibition of phosphodiesterases (PDEs), and modulation of toll-like receptors (TLR). METHODS: Lipopolysaccharide-activated cord blood monocytes (CBM) from 19 infants were exposed to caffeine (0-200 µmol/l) with or without previous exposure to A1R, A3R, or PDE IV antagonists to determine changes in dose-response curves. Cytokines levels (enzyme-linked immunosorbent assay (ELISA)), intracellular cyclic adenosine monophosphate (cAMP) accumulation (enzyme immunoassay (EIA)), and TLR gene expression (real time qRT PCR) were measured. RESULTS: Caffeine at ≤100 µmol/l decreased TNF-α levels (~25%, P = 0.01) and cAMP. All caffeine concentrations decreased IL-10 levels (17-35%, P < 0.01). A1R, A3R, and PDE blockades decreased TNF-α (31, 21, and 88%, P ≤ 0.01), but not IL-10. Caffeine further decreased TNF-α following A3R and PDE blockades. Caffeine concentrations directly correlated to TLR4 gene expression (r = 0.84; P < 0.001). CONCLUSION: Neither A3R, nor PDE blockades are involved in caffeine's modulation of cytokine release by CBM at any concentration. Besides A1R blockade, caffeine's upregulation of TLR4 may promote inflammation at high concentrations.

PREOXYGENATION: COULD SAFETY MEASURE BE MADE LESS DANGEROUS?.

While providing reserve time for dificult airway management, preoxygenation with pure oxygen increases the risk of pulmonary complications due to absorption atelectases. The authors explored when it could be appropriate to prevent atelectases by preoxygenation with decreased FiO2. ASA I-II elective gynecological surgery patients were randomized among five groups (n = 22 each) with preoxygenation using FiO2 100, 70, 60, 60% + PEEP 5 mbar and 50%. Even FiO2 70% led to decrease. in safe apnea time (i.e. time interval to Sp²O2 95%) by two, while FiO2 50% - by more than three times. Furthermore, in five similar additional groups of women with same techniques ofpreoxygenation (n = 10 each) it was shown that for FiO2 5 70% very fast pattern of SpO2 fall after the first change ofpulseoxymeter figure (100% by 99%) is typical: interval to SpO2 90% was less than 1 min, while for FiO2 100% it lasts for 200 s. Since critical problem is "Cannot intubate, cannot ventilate", the authors tried to focus on the difficultfacemask ventilation prognosis. In the group of 71 elective general surgery patients (31 males, 40 females, ASA I-III) original prognostic model based on seven simple bedside tests (removable dentures, beard, snoring, Mallampati class 2-4, age > 50 y.o., BM > 30 kg/m², sternomental distance < 12 cm) demonstrated the reliability of difficult facemask ventilation negative prognosis of 97,5%. The authors suggest that only in patients with reliable prognosis of easy facemask ventilation prevention ofpulmonary complications by preoxygenation with FiO2 50-60% could be safely recommended.