Strengthening Altitude Knowledge: A Delphi Study to Define Minimum Knowledge of Altitude Illness for Laypersons Traveling to High Altitude.

Berendsen, Remco R., Peter Bärtsch, Buddha Basnyat, Marc Moritz Berger, Peter Hackett, Andrew M. Luks, Jean-Paul Richalet, Ken Zafren, Bengt Kayser, and the STAK Plenary Group. Strengthening altitude knowledge: a Delphi study to define minimum knowledge of altitude illness for laypersons traveling to high altitude. High Alt Med Biol. 23:330-337, 2022. Introduction: A lack of knowledge among laypersons about the hazards of high-altitude exposure contributes to morbidity and mortality from acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) among high-altitude travelers. There are guidelines regarding the recognition, prevention, and treatment of acute-altitude illness for experts, but essential knowledge for laypersons traveling to high altitudes has not been defined. We sought expert consensus on the essential knowledge required for people planning to travel to high altitudes. Methods: The Delphi method was used. The panel consisted of two moderators, a core expert group and a plenary expert group. The moderators made a preliminary list of statements defining the desired minimum knowledge for laypersons traveling to high altitudes, based on the relevant literature. These preliminary statements were then reviewed, supplemented, and modified by a core expert group. A list of 33 statements was then presented to a plenary group of experts in successive rounds. Results: It took three rounds to reach a consensus. Of the 10 core experts invited, 7 completed all the rounds. Of the 76 plenary experts, 41 (54%) participated in Round 1, and of these 41 a total of 32 (78%) experts completed all three rounds. The final list contained 28 statements in 5 categories (altitude physiology, sleeping at altitude, AMS, HACE, and HAPE). This list represents an expert consensus on the desired minimum knowledge for laypersons planning high-altitude travel. Conclusion: Using the Delphi method, the STrengthening Altitude Knowledge initiative yielded a set of 28 statements representing essential learning objectives for laypersons who plan to travel to high altitudes. This list could be used to develop educational interventions.

Prevention of vasoplegia with CytoSorb in heart failure patients undergoing cardiac surgery (CytoSorb-HF trial): protocol for a randomised controlled trial.

INTRODUCTION: Vasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac output. The pathophysiology is complex and includes the systemic inflammatory response caused by cardiopulmonary bypass (CPB) and surgical trauma. Patients with end-stage heart failure (HF) are at increased risk for developing vasoplegia. The CytoSorb adsorber is a relatively new haemoadsorption device which can remove circulating inflammatory mediators in a concentration based manner. The CytoSorb-HF trial aims to evaluate the efficacy of CytoSorb haemoadsorption in limiting the systemic inflammatory response and preventing postoperative vasoplegia in HF patients undergoing cardiac surgery with CPB. METHODS AND ANALYSIS: This is an investigator-initiated, single-centre, randomised, controlled clinical trial. In total 36 HF patients undergoing elective cardiac surgery with an expected CPB duration of more than 120 min will be randomised to receive CytoSorb haemoadsorption along with standard surgical treatment or standard surgical treatment alone. The primary endpoint is the change in systemic vascular resistance index with phenylephrine challenge after CPB. Secondary endpoints include inflammatory markers, sublingual microcirculation parameters and 30-day clinical indices. In addition, we will assess the cost-effectiveness of using the CytoSorb adsorber. Vascular reactivity in response to phenylephrine challenge will be assessed after induction, after CPB and on postoperative day 1. At the same time points, and before induction and on postoperative day 4 (5 time points in total), blood samples will be collected and the sublingual microcirculation will be recorded. Study participants will be followed up until day 30. ETHICS AND DISSEMINATION: The trial protocol was approved by the Medical Ethical Committee of Leiden The Hague Delft (METC LDD, registration number P20.039). The results of the trial will be published in peer-reviewed medical journals and through scientific conferences. TRIAL REGISTRATION NUMBER: NCT04812717.

Voluntary Increase of Minute Ventilation for Prevention of Acute Mountain Sickness.

This study evaluated the feasibility and efficacy of voluntary sustained hyperventilation during rapid ascent to high altitude for the prevention of acute mountain sickness (AMS). Study subjects (n=32) were volunteer participants in a 2-day expedition to Mount Leoneras (4954 m), starting at 2800m (base camp at 4120 m). Subjects were randomized to either: 1) an intervention group using the voluntary hyperventilation (VH) technique targeting an end-tidal CO2 (ETCO2)<20 mmHg; or 2) a group using acetazolamide (AZ). During the expedition, respiratory rate (28±20 vs. 18±5 breaths/min, mean±SD, P<0.01) and SpO2 (95%±4% vs. 89%±5%, mean±SD, P<0.01) were higher, and ETCO2 (17±4 vs. 26±4 mmHg, mean±SD, P<0.01) was lower in the VH group compared to the AZ group - as repeatedly measured at equal fixed intervals during the ascent - showing the feasibility of the VH technique. Regarding efficacy, the incidence of 6 (40%) subjects registering an LLS score≥3 in the VH group was non-inferior to the 3 (18%) subjects in the acetazolamide group (P=0.16, power 28%). Voluntary increase in minute ventilation is a feasible technique, but - despite the underpowered non-inferiority in this small-scale proof-of-concept trial - it is not likely to be as effective as acetazolamide to prevent AMS.

Preoperative anaemia and outcome after elective cardiac surgery: a Dutch national registry analysis.

BACKGROUND: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. METHODS: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. RESULTS: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4-1.9; P<0.001). The risk of 120-day mortality increased with anaemia severity (mild anaemia aOR 1.6; 95% CI: 1.3-1.9; P<0.001; and moderate-to-severe anaemia aOR 1.8; 95% CI: 1.4-2.4; P<0.001). Preoperative anaemia was associated with red blood cell transfusion and postoperative morbidity, the causes of which included renal failure, pneumonia, and myocardial infarction. CONCLUSIONS: Preoperative anaemia was associated with mortality and morbidity after cardiac surgery. The risk of adverse outcomes increased with anaemia severity. Preoperative anaemia is a potential target for treatment to improve postoperative outcomes.

Incidence and risk factors of unplanned emergency department visits following thoracic surgery.

Background: Unplanned visits for care following a surgical procedure can represent a lapse in quality of care. The purpose of this study was to define the proportion of patients undergoing thoracic surgery who return to the emergency department (ED) within 6 months after discharge and the reasons for the returns. In addition, the risk factors for ED visits after thoracic surgery were identified. Methods: All adult patients undergoing thoracic surgery at the Leiden University Medical Center between January 1, 2016, and December 31, 2017, were reviewed. To identify potential risk factors for ED return visits, a multivariate regression analysis was performed. A subgroup analysis of patients who reported pain during the ED visit was performed to identify the risk factors for pain-related return to the ED. Results: Of 277 patients who underwent thoracic surgery, 27.4% (n = 76) returned to the ED within 6 months after discharge. Among these patients, 41 (53.9%) presented with postoperative pain. Younger patients (odds ratio [OR], 0.98; P = .04), those who were operated on through a thoracotomy (OR, 2.92; P = .04), and those reporting a high pain score on the ward (OR, 1.98; P < .001) were at increased risk of returning to the ED. Conclusions: The rate of patients returning to the ED after thoracic surgery was high. Pain was the most frequently reported reason for unplanned ED visits. The results of this study highlight the need to optimize the postoperative care and the follow-up of patients undergoing thoracic surgery.

Vasoresponsiveness in patients with heart failure (VASOR): protocol for a prospective observational study.

BACKGROUND: Vasoplegia is a severe complication which may occur after cardiac surgery, particularly in patients with heart failure. It is a result of activation of vasodilator pathways, inactivation of vasoconstrictor pathways and the resistance to vasopressors. However, the precise etiology remains unclear. The aim of the Vasoresponsiveness in patients with heart failure (VASOR) study is to objectify and characterize the altered vasoresponsiveness in patients with heart failure, before, during and after heart failure surgery and to identify the etiological factors involved. METHODS: This is a prospective, observational study conducted at Leiden University Medical Center. Patients with and patients without heart failure undergoing cardiac surgery on cardiopulmonary bypass are enrolled. The study is divided in two inclusion phases. During phase 1, 18 patients with and 18 patients without heart failure are enrolled. The vascular reactivity in response to a vasoconstrictor (phenylephrine) and a vasodilator (nitroglycerin) is assessed in vivo on different timepoints. The response to phenylephrine is assessed on t1 (before induction), t2 (before induction, after start of cardiotropic drugs and/or vasopressors), t3 (after induction), t4 (15 min after cessation of cardiopulmonary bypass) and t5 (1 day post-operatively). The response to nitroglycerin is assessed on t1 and t5. Furthermore, a sample of pre-pericardial fat tissue, containing resistance arteries, is collected intraoperatively. The ex vivo vascular reactivity is assessed by constructing concentrations response curves to various vasoactive substances using isolated resistance arteries. Next, expression of signaling proteins and receptors is assessed using immunohistochemistry and mRNA analysis. Furthermore, the groups are compared with respect to levels of organic compounds that can influence the cardiovascular system (e.g. copeptin, (nor)epinephrine, ANP, BNP, NTproBNP, angiotensin II, cortisol, aldosterone, renin and VMA levels). During inclusion phase 2, only the ex vivo vascular reactivity test is performed in patients with (N = 12) and without heart failure (N = 12). DISCUSSION: Understanding the difference in vascular responsiveness between patients with and without heart failure in detail, might yield therapeutic options or development of preventive strategies for vasoplegia, leading to safer surgical interventions and improvement in outcome. TRIAL REGISTRATION: The Netherlands Trial Register (NTR), NTR5647. Registered 26 January 2016.

Vasoplegia After Surgical Left Ventricular Restoration: 2-Year Follow-Up.

BACKGROUND: Vasoplegia is a severe complication that can develop after surgical procedures for heart failure. The current study evaluated the effect of vasoplegia on survival, cardiac function, and renal function 2 years after surgical left ventricular restoration (SVR). METHODS: Heart failure patients with a left ventricular ejection fraction (LVEF) of 0.35 or less who underwent SVR in 2006 to 2014 were included. Vasoplegia was defined as the continuous need of vasopressors (norepinephrine ≥0.2 µg · kg-1 · min-1 or terlipressin [any dose], or both) combined with a cardiac index of 2.2 L · min-1 · m-2 or higher for at least 12 consecutive hours, starting within the first 3 days postoperatively. The effect of vasoplegia on mortality, New York Heart Association Functional Classification, LVEF, and creatinine clearance was assessed up to 2 years of follow-up. RESULTS: SVR was performed in 113 patients (80% men), aged 62 ± 10 years, and with an LVEF of 0.25 ± 0.06. Postoperative vasoplegia developed in 23%. Survival was lower in patients with vasoplegia compared with patients without vasoplegia at 6 months (62% vs 90%, p = 0.001) and at 2 years (50% versus 84%, p < 0.001). At the 2-year follow-up, New York Heart Association class and LVEF had improved and were similar in both groups (respectively, p = 0.319 and p = 0.444). Creatinine clearance was lower in patients with vasoplegia compared with patients without vasoplegia 2 years postoperatively (p < 0.001), even after correcting for baseline creatinine clearance (p = 0.009). CONCLUSIONS: Vasoplegia after SVR is associated with decreased survival. Despite an improved and similar cardiac function, renal function was compromised in vasoplegic patients at the 2-year follow-up.

Electronic Nose Technology Fails to Sniff Out Acute Mountain Sickness.

Berendsen, Remco R., Marieke E. van Vessem, Marcel Bruins, Luc J.S.M. Teppema, Leon P.H.J. Aarts, and Bengt Kayser. Electronic nose technology fails to sniff out acute mountain sickness. High Alt Med Biol. 19:232-236, 2018. AIM: The aim of the study was to evaluate whether an electronic nose can discriminate between individuals with and without acute mountain sickness (AMS) following rapid ascent to 4554 m. RESULTS: We recruited recreational climbers (19 women, 82 men; age 35 ± 10 years, mean ± standard deviation [SD]) upon arrival at 4554 m (Capanna Regina Margherita, Italy) for a proof of concept study. AMS was assessed with the Lake Louise self-report score (LLSRS) and the abbreviated Environmental Symptoms Questionnaire (ESQc); scores ≥3 and ≥0.7 were considered AMS, respectively. Exhaled air was analyzed with an electronic nose (Aeonose; The eNose Company, Netherlands). The collected data were analyzed using an artificial neural network. AMS prevalence was 44% with the LLSRS (mean score of those sick 4.4 ± 1.4 [SD]) and 20% with the ESQc (1.2 ± 0.5). The electronic nose could not discriminate between AMS and no AMS (LLSRS p = 0.291; ESQc p = 0.805). CONCLUSION: The electronic nose technology utilized in this study could not discriminate between climbers with and without symptoms of AMS in the setting of an acute exposure to an altitude of 4554 m. At this stage, we cannot fully exclude that this technology per se is not able to discriminate for AMS. The quest for objective means to diagnose AMS thus continues.

Incidence and predictors of vasoplegia after heart failure surgery.

Objectives: Vasoplegia has been described as a complication after cardiac surgery, particularly in patients with a poor left ventricular ejection fraction. The aim of this study was to assess the incidence, survival and predictors of vasoplegia in patients undergoing heart failure surgery and to propose a risk model. Methods: A retrospective study including heart failure patients who underwent surgical left ventricular restoration, CorCap implantation or left ventricular assist device implantation between 2006 and 2015. Patients were classified by the presence or absence of vasoplegia. Results: Two hundred and twenty-five patients were included. The incidence of vasoplegia was 29%. The 90-day survival rate in vasoplegic patients was lower compared with non-vasoplegic patients (71% vs 91%, P < 0.001). After adjusting for age, sex and surgical procedure, anaemia (OR 2.195; 95% CI 1.146, 4.204; P = 0.018) and a higher thyroxine level (OR 1.140; 95% CI 1.033, 1.259; P = 0.009) increased the risk of vasoplegia; a higher creatinine clearance (OR 0.980; 95% CI 0.965, 0.994; P = 0.006) and beta-blocker use (OR 0.257; 95% CI 0.112, 0.589; P = 0.001) decreased the risk. The risk model consisted of the same variables and could adequately identify patients at risk for vasoplegia. Conclusions: Vasoplegia after heart failure surgery is common and results in a lower survival rate. Anaemia and a higher thyroxine level are associated with an increased risk on vasoplegia. In contrast, a higher creatinine clearance and beta-blocker use decrease the risk on vasoplegia. These factors are used in the risk model that may guide treatment strategy.

Erythropoietin does not have effects on the ventilatory and pulmonary vascular response to acute hypoxia in men and women.

NEW FINDINGS: What is the central question of this study? Does a clinically relevant intravenous dose of erythropoeitin affect the hypoxic ventilatory response and/or hypoxic pulmonary vasoconstriction in healthy humans? What is the main finding and its importance? Erythropoeitin does not influence the ventilatory and pulmonary vascular responses to acute hypoxia in men or women. Sustained and chronic hypoxia lead to an increase in pulmonary ventilation (hypoxic ventilatory response, HVR) and to an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction, HPV). In this study, we examined the effect of a clinical i.v. dose of recombinant human erythropoietin (50 IU kg-1 ) on the isocapnic HVR and HPV in seven male and seven female subjects by exposing them to hypoxia for 20 min (end-tidal PO2  âˆ¼50 mmHg) while measuring their ventilation and estimating pulmonary arterial pressure from the maximal velocity of the regurgitant jet over the tricuspid valve during systole (ΔPmax ) with echocardiography. In the placebo session, after 5 and 20 min men responded with an increase in ventilation by 0.0056 and 0.0023 l min-1  kg-1   %SpO2-1 , respectively, indicating the presence of hypoxic ventilatory depression. In women, the increase in ventilation was 0.0067 and 0.0047 l min-1  kg-1   %SpO2-1 , respectively. In both sexes, erythropoietin did not alter these responses significantly. In the placebo session, mean ΔPmax increased by 6.1 ± 0.7 mmHg in men (P = 0.035) and by 8.4 ± 1.4 mmHg in women (P = 0.020) during the hypoxic exposure, whereby women had a âˆ¼5 mmHg lower end-tidal PCO2 . Erythropoietin did not alter these responses; in men, ΔPmax increased by 7.5 ± 1.1 mmHg (n.s. versus placebo) and in women by 9.7 ± 2.2 mmHg (n.s. versus placebo). We conclude that women tended to have a greater HPV in placebo conditions and that a clinical dose of erythropoietin has no effect on the HVR and HPV in either sex.

Prosthesis Dislocation After Transapical Valve-In-Valve Mitral Valve Implantation.

Transapical valve-in-valve mitral valve implantation (TA-MVI) has been described as an alternative treatment option in patients with degenerated bioprostheses in the mitral position. We report the first case of prosthesis dislocation and migration into the left atrium after TA-MVI. A new prosthesis was implanted using the same approach. The dislocated prosthesis was successfully removed through the left atrial appendage through an extended anterolateral thoracotomy without the use of cardiopulmonary bypass.

[Treating frostbite injuries]. / Behandeling van bevriezingsletsels.

Frostbite injuries rarely occur in healthy Dutch persons. However, as the number of people engaging in winter and outdoor activities and travelling to high altitudes increases, the risk of frostbite also increases. Frostbite is a cold-induced injury which results from two processes: freezing and microvascular occlusion. Adequate first aid, which focuses on the prevention of refreezing and mechanical injury, and rapid rewarming together with the administration of ibuprofen, are of the greatest importance for limiting eventual tissue damage. Iloprost infusion and possibly (r)tPA are indicated if a patient presents within 24 hours after the tissue has thawed and the injury is such that severe morbidity can be expected. If the patient presents after this time period, hyperbaric oxygen therapy may be considered; however, the evidence available on this type of treatment is limited.

Anesthetic considerations in a patient with amiodarone-induced thyrotoxicosis.

Amiodarone-induced thryrotoxicosis (AIT) is a rare but serious complication of amiodarone use, especially in patients with severe cardiac disease. We present a patient who developed AIT, following administration of amiodarone for life-threatening ventricular arrhythmias. We discuss the medical management of AIT and anesthetic considerations for management of patients with thyrotoxicosis and severe cardiac disease who require surgery including thyroidectomy.