Cerebral blood flow regulation in hypobaric hypoxia: role of haemoconcentration.

During acute hypoxic exposure, cerebral blood flow (CBF) increases to compensate for the reduced arterial oxygen content (CaO2). Nevertheless, as exposure extends, both CaO2 and CBF progressively normalize. Haemoconcentration is the primary mechanism underlying the CaO2 restoration and may therefore explain, at least in part, the CBF normalization. Accordingly, we tested the hypothesis that reversing the haemoconcentration associated with extended hypoxic exposure returns CBF towards the values observed in acute hypoxia. Twenty-three healthy lowlanders (12 females) completed two identical 4-day sojourns in a hypobaric chamber, one in normoxia (NX) and one in hypobaric hypoxia (HH, 3500 m). CBF was measured by ultrasound after 1, 6, 12, 48 and 96 h and compared between sojourns to assess the time course of changes in CBF. In addition, CBF was measured at the end of the HH sojourn after hypervolaemic haemodilution. Compared with NX, CBF was increased in HH after 1 h (P = 0.001) but similar at all later time points (all P > 0.199). Haemoglobin concentration was higher in HH than NX from 12 h to 96 h (all P < 0.001). While haemodilution reduced haemoglobin concentration from 14.8 ± 1.0 to 13.9 ± 1.2 g·dl-1 (P < 0.001), it did not increase CBF (974 ± 282 to 872 ± 200 ml·min-1; P = 0.135). We thus conclude that, at least at this moderate altitude, haemoconcentration is not the primary mechanism underlying CBF normalization with acclimatization. These data ostensibly reflect the fact that CBF regulation at high altitude is a complex process that integrates physiological variables beyond CaO2. KEY POINTS: Acute hypoxia causes an increase in cerebral blood flow (CBF). However, as exposure extends, CBF progressively normalizes. We investigated whether hypoxia-induced haemoconcentration contributes to the normalization of CBF during extended hypoxia. Following 4 days of hypobaric hypoxic exposure (corresponding to 3500 m altitude), we measured CBF before and after abolishing hypoxia-induced haemoconcentration by hypervolaemic haemodilution. Contrary to our hypothesis, the haemodilution did not increase CBF in hypoxia. Our findings do not support haemoconcentration as a stimulus for the CBF normalization during extended hypoxia.

Personal Protective Equipment Protocols Lead to a Delayed Initiation of Patient Assessment in Mountain Rescue Operations.

van Veelen, Michiel J., Giulia Roveri, Ivo B. Regli, Tomas Dal Cappello, Anna Vögele, Michela Masè, Marika Falla, and Giacomo Strapazzon. Personal protective equipment protocols lead to a delayed initiation of patient assessment in mountain rescue operations. High Alt Med Biol. 24:127-131, 2023. Introduction: Mountain rescue operations can be challenging in austere environmental conditions and remote settings. Airborne infection prevention measures include donning of personal protective equipment (PPE), potentially delaying the approach to a patient. We aimed to investigate the time delay caused by these prevention measures. Methods: This randomized crossover trial consisted of 24 rescue simulation trials intended to be as realistic as possible, performed by mountain rescue teams in difficult terrain. We analyzed the time needed to perform an airborne infection prevention protocol during the approach to a patient. Time delays in scenarios involving patients already wearing versus not wearing face masks and gloves were compared using a linear mixed model Results: The airborne infection prevention measures (i.e., screening questionnaire, hand antisepsis, and donning of PPE) resulted in a time delay of 98 ± 48 (26-214) seconds on initiation of patient assessment. There was a trend to a shorter time to perform infection prevention measures if the simulated patient was already wearing PPE consisting of face mask and gloves (p = 0.052). Conclusion: Airborne infection prevention measures may delay initiation of patient assessment in mountain rescue operations and could impair clinical outcomes in time-sensitive conditions. Trial registration number 0105095-BZ Ethics Committee review board of Bolzano.

Effects of Hypobaric Hypoxia on Coagulation in Healthy Subjects Exposed to 3,500 m Altitude.

Kammerer, Tobias, Anna Walzl, Thomas Müller, Philipp Groene, Giulia Roveri, Rachel Turner, Johanna Roche, Hannes Gatterer, Christoph Siebenmann, and Simon T. Schäfer. Effects of hypobaric hypoxia on coagulation in healthy subjects exposed to 3,500 m altitude. High Alt Med Biol. 24:94-103, 2023. Background: Hypoxia is discussed as a trigger for prothrombotic changes both in intensive care and high altitude medicine. This research study aimed to evaluate the effect of isolated hypobaric hypoxia (HH) on coagulation in females in a highly standardized setting. Methods: Twelve healthy female subjects were studied under HH (equivalent to 3,500 m) and normoxia (NX) during two 4-day sojourns, in a strictly controlled crossover design. Nutrition, fluid intake, hormonal status (i.e., menstrual cycle variation), and physical stress were standardized. Functional coagulation and blood lysis were measured by viscoelastometry and compared between HH and NX. In addition, plasma-based coagulation tests (PBCTs), namely prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII coagulation activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), and von Willebrand factor ristocetin cofactor activity (vWF:RCo) were measured. Results: Neither for Viscoelastic Haemostatic Assays nor for PBCTs significant changes were found for HH compared with NX (all p > 0.05). Specifically, the lysis ability, as well as clotting time, clot formation, clot amplitude, and maximum clot firmness unchanged were similar between HH and NX. This also applied to all other variables. Conclusion: We demonstrate that moderate HH per se has no influence on blood coagulation in healthy females.

Occupational Accidents Among Search and Rescue Providers During Mountain Rescue Operations and Training Events.

STUDY OBJECTIVE: We analyzed occupational accidents reported among Corpo Nazionale Soccorso Alpino e Speleologico (CNSAS) providers during mountain search and rescue operations and training events in Italy (1999 to 2019). METHODS: We extracted anonymized data from the CNSAS accident database for all cases of injured mountain search and rescue providers that activated CNSAS insurance (1999 to 2019). We report epidemiological characteristics, mechanisms, type, and severity of injury or illness, clinical outcome, and recovery time. RESULTS: A total of 784 cases of injuries in CNSAS mountain search and rescue providers were recorded. Forty-one percent of the cases occurred during rescue operations and 59% during training events. Overall, trauma was the main cause of injury (96%), whereas only 4% of the cases were classified as medical or environmental illnesses. Moderate injury (National Advisory Committee for Aeronautics II to III) occurred in 80% of the reported accidents. Recovery time differed based on the degree of accident severity. Fatalities occurred in 2% of the cases reported and occurred during rescue operations only. CONCLUSION: In this long-term retrospective analysis, we showed that accidents occurred among mountain search and rescue providers both during rescue operations and training events. Given the high prevalence and associated costs, it is of pivotal importance to understand the epidemiology and characteristics of occupational injury and illness among this out-of-hospital workforce to better inform future prevention strategies.

Drones reduce the treatment-free interval in search and rescue operations with telemedical support - A randomized controlled trial.

INTRODUCTION: Response to medical incidents in mountainous areas is delayed due to the remote and challenging terrain. Drones could assist in a quicker search for patients and can facilitate earlier treatment through delivery of medical equipment. We aim to assess the effects of using drones in search and rescue (SAR) operations in challenging terrain. We hypothesize that drones can reduce the search time and treatment-free interval of patients by delivering an emergency kit and telemedical support. METHODS: In this randomized controlled trial with a cross-over design two methods of searching for and initiating treatment of a patient were compared. The primary outcome was a comparison of the times for locating a patient through visual contact and starting treatment on-site between the drone-assisted intervention arm and the conventional ground-rescue control arm. A linear mixed model (LMM) was used to evaluate the effect of using a drone on search and start of treatment times. RESULTS: Twenty-four SAR missions, performed by six SAR teams each with four team members, were analyzed. The mean time to locate the patient was 14.6 min (95% CI 11.3-17.9) in the drone-assisted intervention arm and 20.6 min (95% CI 17.3-23.9) in the control arm. The mean time to start treatment was 15.7 min (95% CI 12.4-19.0) in the drone-assisted arm and 22.4 min (95% CI 19.1-25.7) in the control arm (p < 0.01 for both comparisons). CONCLUSION: The successful use of drones in SAR operations leads to a reduction in search time and treatment-free interval of patients in challenging terrain, which could improve outcomes in patients suffering from traumatic injuries, the most commonly occurring incident requiring mountain rescue operations.

Changes in body mass, appetite-related hormones, and appetite sensation in women during 4 days of hypobaric hypoxic exposure equivalent to 3,500-m altitude.

Altitude exposure may suppress appetite and hence provide a viable weight-loss strategy. While changes in food intake and availability as well as physical activity may contribute to altered appetite at altitude, herein we aimed to investigate the isolated effects of hypobaric hypoxia on appetite regulation and sensation. Twelve healthy women (age: 24.0 ± 4.2 years, body mass: 60.6 ± 7.0 kg) completed two 4-day sojourns in a hypobaric chamber, one in normoxia [PB = 761 mmHg, 262 m (NX)] and one in hypobaric hypoxia [PB = 493 mmHg (HH)] equivalent to 3,500-m altitude. Energy intake was standardized 4 days prior and throughout both sojourns. Plasma concentrations of leptin, acylated ghrelin, cholecystokinin (CCK), and cytokine growth differentiation factor 15 (GDF15) were determined every morning. Before and after breakfast, lunch, and dinner, appetite was assessed using visual analog scales. Body mass was significantly decreased following HH but not NX (-0.71 ± 0.32 kg vs. -0.05 ± 0.54 kg, condition: P < 0.001). Compared to NX, acylated ghrelin decreased throughout the HH sojourn (condition × time: P = 0.020), while leptin was higher throughout the entire HH sojourn (condition: P < 0.001). No differences were observed in CCK and GDF15 between the sojourns. Feelings of satiety and fullness were higher (condition: P < 0.001 and P = 0.013, respectively), whereas prospective food consumption was lower in HH than in NX (condition: P < 0.001). Our findings suggest that hypoxia exerts an anorexigenic effect on appetite-regulating hormones, suppresses subjective appetite sensation, and can induce weight loss in young healthy women. Among the investigated hormones, acylated ghrelin and leptin most likely explain the observed HH-induced appetite suppression.NEW & NOTEWORTHY This study investigated the effects of hypoxia on appetite regulation in women while strictly controlling for diet, physical activity, menstrual cycle, and environmental conditions. In young women, 4 days of altitude exposure (3,500 m) decreases body weight and circulating acylated ghrelin levels while preserving leptin concentrations. In line with the hormonal changes, altitude exposure induces alterations in appetite sensation, consisting of a decreased feeling of hunger and prospective food intake and an increased feeling of fullness and satiety.

Hypobaric hypoxia and cardiac baroreflex sensitivity in young women.

We sought to determine the effects of prolonged moderate hypobaric hypoxia (HH) on cardiac baroreflex sensitivity (cBRS) in young women and whether these effects are a consequence of the reduced arterial oxygen (O2) tension and/or increased pulmonary ventilation in HH. We hypothesized that HH would reduce cBRS and that this effect would be counteracted by acute restoration of the inspiratory partial pressure of O2 ([Formula: see text]) and/or voluntary attenuation of pulmonary ventilation. Twelve healthy women (24.0 ± 4.2 yr) were studied before (day 0) and twice during a sojourn in a hypobaric chamber (∼8 h, day 1; 4 days, day 4) where barometric pressure corresponded to ∼3,500-m altitude. Minute ventilation (V̇e; pneumotachometer), heart rate (electrocardiogram), and arterial pressure (finger volume clamp method) were recorded. cBRS was calculated using transfer function analysis between systolic pressure and RR interval. Assessments were made during 1) spontaneous breathing and (in HH only), 2) controlled breathing (reducing V̇e by ∼1 to 2 L/min), and 3) breathing a hyperoxic gas mixture that normalized [Formula: see text]. During spontaneous breathing, HH decreased cBRS (12.5 ± 7.1, 8.9 ± 4.4, and 7.4 ± 3.0 ms/mmHg on days 0, 1, and 4, respectively; P = 0.018). The normalization of [Formula: see text] increased cBRS (10.6 ± 3.3 and 10.7 ± 6.1 ms/mmHg on days 1 and 4) in HH compared with values observed during spontaneous breathing (P < 0.001), whereas controlled breathing had no effect on cBRS (P = 0.708). These findings indicate that ongoing arterial chemoreflex activation by the reduced arterial O2 tension, independently of the hypoxic ventilatory response, reduces cBRS in young women exposed to extended HH.NEW & NOTEWORTHY We examined the effects of prolonged hypobaric hypoxia (corresponding to ∼3,500-m altitude) on cardiac baroreflex sensitivity (cBRS) in young women and investigated underlying mechanisms. We found that cBRS was reduced in hypoxia and that this reduction was attenuated by acute restoration of inspiratory oxygen partial pressure but not by volitional restraint of pulmonary ventilation. These findings help to elucidate the role of arterial chemoreflex mechanisms in the control of cBRS during hypobaric hypoxia in young women.

Hypoxia briefly increases diuresis but reduces plasma volume by fluid redistribution in women.

We have recently reported that hypobaric hypoxia (HH) reduces plasma volume (PV) in men by decreasing total circulating plasma protein (TCPP). Here, we investigated whether this applies to women and whether an inflammatory response and/or endothelial glycocalyx shedding could facilitate the TCCP reduction. We further investigated whether acute HH induces a short-lived diuretic response that was overlooked in our recent study, where only 24-h urine volumes were evaluated. In a strictly controlled crossover protocol, 12 women underwent two 4-day sojourns in a hypobaric chamber: one in normoxia (NX) and one in HH equivalent to 3,500-m altitude. PV, urine output, TCPP, and markers for inflammation and glycocalyx shedding were repeatedly measured. Total body water (TBW) was determined pre- and postsojourns by deuterium dilution. PV was reduced after 12 h of HH and thereafter remained 230-330 mL lower than in NX (P < 0.0001). Urine flow was 45% higher in HH than in NX throughout the first 6 h (P = 0.01) but lower during the second half of the first day (P < 0.001). Twenty-four-hour urine volumes (P ≥ 0.37) and TBW (P ≥ 0.14) were not different between the sojourns. TCPP was lower in HH than in NX at the same time points as PV (P < 0.001), but inflammatory or glycocalyx shedding markers were not consistently increased. As in men, and despite initially increased diuresis, HH-induced PV contraction in women is driven by a loss of TCPP and ensuing fluid redistribution, rather than by fluid loss. The mechanism underlying the TCPP reduction remains unclear but does not seem to involve inflammation or glycocalyx shedding.NEW & NOTEWORTHY This study is the first to investigate the mechanisms underlying plasma volume (PV) contraction in response to hypoxia in women while strictly controlling for confounders. PV contraction in women has a similar time course and magnitude as in men and is driven by the same mechanism, namely, oncotically driven redistribution rather than loss of fluid. We further report that hypoxia facilitates an increase in diuresis, that is, however, short-lived and of little relevance for PV regulation.

Effect of Wearing Personal Protective Equipment (PPE) on CPR Quality in Times of the COVID-19 Pandemic-A Simulation, Randomised Crossover Trial.

Cardiopulmonary resuscitation (CPR) is considered an aerosol-generating procedure. Consequently, COVID-19 resuscitation guidelines recommend the use of personal protective equipment (PPE) during resuscitation. In this simulation of randomised crossover trials, we investigated the influence of PPE on the quality of chest compressions (CCs). Thirty-four emergency medical service BLS-providers performed two 20 min CPR sequences (five 2 min cycles alternated by 2 min of rest) on manikins, once with and once without PPE, in a randomised order. The PPE was composed of a filtering facepiece 3 FFP3 mask, safety glasses, gloves and a long-sleeved gown. The primary outcome was defined as the difference between compression depth with and without PPE; secondary outcomes were defined as differences in CC rate, release and the number of effective CCs. The participants graded fatigue and performance, while generalised estimating equations (GEE) were used to analyse data. There was no significant difference in CC quality between sequences without and with PPE regarding depth (mean depth 54 ± 5 vs. 54 ± 6 mm respectively), rate (mean rate 119 ± 9 and 118 ± 6 compressions per minute), release (mean release 2 ± 2 vs. 2 ± 2 mm) and the number of effective CCs (43 ± 18 vs. 45 ± 17). The participants appraised higher fatigue when equipped with PPE in comparison to when equipped without PPE (p < 0.001), and lower performance was appraised when equipped with PPE in comparison to when equipped without PPE (p = 0.031). There is no negative effect of wearing PPE on the quality of CCs during CPR in comparison to not wearing PPE.

Calcium priming of the central venous catheter prevents a drop in ionized calcium concentration during Regional Citrate Anticoagulation.

During citrate-based Continuous Renal Replacement Therapy (CRRT), an infusion of calcium is necessary to replace the calcium lost in the effluent. The replacement takes place through a central venous catheter (CVC) that is primed with saline solution. Thus, we hypothesized a potential systemic anticoagulation caused by the unchelated citrate reaching the patient at the start of CRRT because of 0.42 ml of line dead space. In this pilot study, two subpopulations of 7 patients who underwent Continuous Veno-Venous Hemodiafiltration (150 ml/min of blood flow, 1500 ml/h dialysate flow, 1500 ml/h of citrate predilution) were studied. One had the CVC primed with saline, the second with calcium chloride 10%. Calcium replacement rate was 6.3 ± 0.2 ml/h. Ionized calcium concentration was studied over time in the two groups and in the group with saline priming we detected a transient period of hypocalcemia (ionized calcium concentration [iCa] < 1.00 mmol/l for the first 2 hours). In the subpopulation with the calcium priming, this was not present. No significant effect on filter life emerged. Priming of the catheter with calcium seems effective in avoiding a potential issue regarding citrate accumulation at the start of CRRT. More studies are needed to assess the clinical significance of this finding.

Drugs and acute porphyrias: reasons for a hazardous relationship.

The porphyrias are a group of metabolic diseases caused by inherited or acquired enzymatic deficiency in the metabolic pathway of heme biosynthesis. Simplistically, they can be considered as storage diseases, because the partial enzymatic defect gives rise to a metabolic "bottleneck" in the biosynthetic pathway and hence to an accumulation of different metabolic intermediates, potentially toxic and responsible for the various (cutaneous or neurovisceral) clinical manifestations observed in these diseases. In the acute porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and the very rare delta-aminolevulinic acid dehydratase ALAD-d porphyria), the characteristic severe neurovisceral involvement is mainly ascribed to a tissue accumulation of delta-aminolevulinic acid, a neurotoxic nonporphyrin precursor. Many different factors, both endogenous and exogenous, may favor the accumulation of this precursor in patients who are carriers of an enzymatic defect consistent with an acute porphyria, thus contributing to trigger the serious (and potentially fatal) clinical manifestations of the disease (acute porphyric attacks). To date, many different drugs are known to be able to precipitate an acute porphyric attack, so that the acute porphyrias are also considered as pharmacogenetic or toxygenetic diseases. This article reviews the different biochemical mechanisms underlying the capacity of many drugs to precipitate a porphyric acute attack (drug porphyrogenicity) in carriers of genetic mutations responsible for acute porphyrias, and addresses the issue of prescribing drugs for patients affected by these rare, but extremely complex, diseases.