Non-invasive evaluation of new-onset atrial fibrillation after cardiac surgery: a protocol for the BigMap study.

AIMS: New-onset atrial fibrillation (NOAF) is the most common complication after cardiac surgery, occurring in 25-50% of patients. It is associated with post-operative stroke, increased mortality, prolonged hospital length of stay, and higher treatment costs. Previous small observational studies have identified the left atrium as a source of the electrical rotors and foci maintaining NOAF, but confirmation by a large prospective clinical study is still missing. The aim of the proposed study is to investigate whether the source of NOAF lies in the left atrium. The correct identification of NOAF-maintaining structures in cardiac surgical patients might offer potential therapeutic targets for prophylactic perioperative ablation strategies. METHODS AND RESULTS: This is a prospective single-centre observational study of patients developing NOAF after cardiac surgery. The primary outcome is the description of NOAF-maintaining structures within the atria. Key secondary outcomes include overall mortality, intensive care unit length of stay, hospital-ventilator-free days, and proportion of persistent NOAF. In NOAF patients, the non-invasive electrophysiological mapping will be conducted using a 252-electrode electrocardiogram vest. After mapping, a low-dose computed tomography scan of the chest will be performed to integrate the electrophysiological mapping results into a 3D picture of the heart. The study will include approximately 570 patients, of whom 30% (n = 170) are expected to develop NOAF. Sample size calculation revealed that 157 NOAF patients are necessary to assess the primary outcome. Patients will be tracked for a total of 5 years. CONCLUSIONS: This is the largest prospective study to date describing the electrophysiological mechanisms of NOAF using non-invasive mapping.

Low dose radiation therapy for severe COVID-19 pneumonia: a randomized double-blind study.

PURPOSE: The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low dose radiation therapy (LDRT) in this patient cohort. METHODS AND MATERIALS: Patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and ICU clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days (VFDs) at day 15 post-intervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers. RESULTS: Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day VFDs was observed between groups (p = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm, and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95%CI, 40.7-99.5%) in both arms (p = 0.69). Apart from a more pronounced reduction in lymphocyte counts following LDRT (p < 0.01), analyses of secondary endpoints revealed no significant differences between the groups. CONCLUSIONS: Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

5-year results of a newly implemented mechanical circulatory support program for terminal heart failure patients in a Swiss non-cardiac transplant university hospital.

BACKGROUND: In Switzerland, long-term circulatory support programs have been limited to heart transplant centers. In 2014, to improve the management of patients with end-stage heart failure not eligible for transplantation, we implemented a left ventricular assist device (LVAD) program for destination therapy at the University Hospital of Basel. METHODS: We described the program set-up with practical aspects. Patients aged 65 and above with therapy refractory end-stage heart failure without major contraindication for LVAD implantation were included. Younger patients with bridge-to-candidacy profile were also considered. Using the Kaplan-Meier estimate, we retrospectively analyzed the overall survival and freedom from major adverse events after LVAD implantation. We compared our results to internationally reported data. RESULTS: Between October 2014 and September 2019, 16 patients received an LVAD in our center. The mean age at implantation was 67.1 years. The mean EuroSCORE II was 24.4% and the median INTERMACS level was 4. Thirteen patients received an LVAD as destination therapy and three patients as bridge-to-candidacy. The overall survival was 87.5 and 70% at 1 and 2 years, respectively. Freedom from stroke was 81.3% at 1 and 2 years. Freedom from device infection was 67.7 and 58.7% at 1 and 2 years, respectively. Freedom from gastrointestinal bleeding was 75 and 56.3% at 1 and 2 years, respectively. Freedom from readmission was 50 and 31.3% and at 6 months and 1 year, respectively. CONCLUSIONS: The Basel experience demonstrated the possible implementation of an LVAD program for destination therapy or bridge-to-candidacy in a non-transplant comprehensive heart-failure center with midterm survival results and freedom from major adverse events comparable to international registries. Patient selection remains crucial. TRIAL REGISTRATION: This study was registered on the ClinicalTrials.gov database ( NCT04263012 ).

Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia: A Randomized Double-Blind Study.

PURPOSE: The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low-dose radiation therapy (LDRT) in this patient cohort. METHODS AND MATERIALS: Patients admitted to the intensive care unit and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and intensive care unit clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days at day 15 postintervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers. RESULTS: Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day ventilator-free days was observed between groups (P = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95% confidence interval, 40.7%-99.5%) in both arms (P = .69). Apart from a more pronounced reduction in lymphocyte counts after LDRT (P < .01), analyses of secondary endpoints revealed no significant differences between the groups. CONCLUSIONS: Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

SARS-CoV-2 outbreak in a tri-national urban area is dominated by a B.1 lineage variant linked to a mass gathering event.

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503.

Systematic screening on admission for SARS-CoV-2 to detect asymptomatic infections.

The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.1%), questioning the cost-benefit ratio of this intervention. Even when the population-wide prevalence was low, the proportion of asymptomatic carriers remained stable, supporting the need for universal infection prevention and control strategies to avoid onward transmission by undetected SARS-CoV-2-carriers during the pandemic.

Advance Directives in the Neurocritically Ill: A Systematic Review.

OBJECTIVES: To determine the frequency of advance directives or directives disclosed by healthcare agents and their influence on decisions to withdraw/withhold life-sustaining care in neurocritically ill adults. DATA SOURCES: PubMed, Embase, and Cochrane databases. STUDY SELECTION: Screening was performed using predefined search terms to identify studies describing directives of neurocritically ill patients from 2000 to 2019. The review was registered prior to the screening process (International Prospective Register of Systematic Reviews identification number 149185). DATA EXTRACTION: Data were collected using standardized forms. Primary outcomes were the frequency of directives and associated withholding/withdrawal of life-sustaining care. DATA SYNTHESIS: Out of 721 articles, 25 studies were included representing 35,717 patients. The number of studies and cohort sizes increased over time. A median of 39% (interquartile range, 14-72%) of patients had directives and/or healthcare agents. The presence of directives was described in patients with stroke, status epilepticus, neurodegenerative disorders, neurotrauma, and neoplasms, with stroke patients representing the largest subgroup. Directives were more frequent among patients with neurodegenerative disorders compared with patients with other illnesses (p = 0.043). In reference to directives, care was adapted in 71% of European, 50% of Asian, and 42% of American studies, and was withheld or withdrawn more frequently over time with a median of 58% (interquartile range, 39-89%). Physicians withheld resuscitation in reference to directives in a median of 24% (interquartile range, 22-70%). CONCLUSIONS: Studies regarding the use and translation of directives in neurocritically ill patients are increasing. In reference to directives, care was adapted in up to 71%, withheld or withdrawn in 58%, and resuscitation was withheld in every fourth patient, but the quality of evidence regarding their effects on critical care remains weak and the risk of bias high. The limited number of patients having directives is worrisome and studies aiming to increase the use and translation of directives are scarce. Efforts need to be made to increase the perception, use, and translation of directives of the neurocritically ill.

Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 Emergence Amidst Community-Acquired Respiratory Viruses.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)-recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs. METHODS: Nasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2. RESULTS: The Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%). CONCLUSIONS: Winter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children.

Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction.

AIMS: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. METHODS AND RESULTS: This article reports the autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. CONCLUSIONS: This study provides an overview of postmortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates among these patients.

Effect of high-dose sodium selenite in cardiac surgery patients: A randomized controlled bi-center trial.

BACKGROUND & AIMS: Cardiac surgery is accompanied by oxidative stress and systemic inflammatory response, which may be associated with organ dysfunction and increased mortality. Selenium and selenoenzymes are important constituents of anti-oxidative defense. We hypothesized that high-dose sodium selenite supplementation can attenuate the postoperative inflammation and might, therefore, improve clinical outcome. METHODS: Randomized, placebo-controlled, double-blinded, bi-center study on 411 adult patients undergoing elective cardiac surgery. Patients received an intravenous bolus of 4000 µg selenium (in the form of sodium selenite) or placebo after induction of anesthesia and 1000 µg/d selenium or placebo during their intensive care unit (ICU) stay. Primary outcome measure was the Sequential Organ Failure Assessment (SOFA) score on the second postoperative day. Secondary endpoints included the change in perioperative selenium levels, change of inflammatory and cardiac markers, use of vasoactive medication, incidence of acute kidney injury, ICU and hospital length of stay, and mortality. RESULTS: The perioperative administration of high-dose sodium selenite prevented the postoperative drop of blood and serum selenium levels, reduced the number of patients depending on postoperative vasoactive support but failed to reduce the postoperative SOFA score and its related organ-specific scores compared to placebo. Except for an increase of postoperative procalcitonin and bilirubin levels in the sodium selenite group, other inflammatory markers, organ function variables and clinical endpoints remained unchanged. CONCLUSIONS: The perioperative administration of high-dose sodium selenite in cardiac surgery patients prevented the postoperative fall of blood selenium levels and reduced the need for postoperative vasoactive support by a yet unknown mechanism. TRIAL REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT01141556.

B-type natriuretic peptide secretion without change in intra-cardiac pressure.

OBJECTIVE: In clinical cardiology, B-type natriuretic peptide (BNP) is used as a non-invasive surrogate marker for intra-cardiac filling pressures, particularly in patients with heart failure. It is unknown whether and to what extent increase in intravascular volume and/or sympathetic tone while maintaining constant intra-cardiac pressures leads to an increase in levels of BNP in vivo. DESIGN AND METHODS: We aimed to test this hypothesis in an experimental in vivo model of patients directly after off-pump coronary artery bypass grafting admitted to the intensive care unit. These patients require high volumes of intravenous fluids titrated to keep intra-cardiac filling pressures and arterial blood pressure in the normal range while awakening from deep general anesthesia. In 27 consecutive patients, intra-cardiac filling pressures (using a pulmonary artery catheter) and levels of BNP were measured simultaneously every 6h. RESULTS: At 0, 6, 12, and 18h, the pulmonary capillary wedge pressure remained constant (12±4, 13±3, 12±3, and 13±3mmHg, respectively; p=0.351). Similarly, right heart filling pressures did not change during the study period. In contrast, BNP levels increased significantly during the study period: Median levels were 82 [IQR 37-162] pg/ml at 0h, 153 [92-246] pg/ml at 6h, 274 [156-392] pg/ml at 12h, and 320 [200-528] pg/ml at 18h (p<0.001). No significant correlation between BNP levels and pulmonary capillary wedge pressures was found (r=0.052; p=0.604). CONCLUSIONS: After cardiac surgery, BNP cannot be considered a reliable non-invasive surrogate for PCWP. In vivo, substantial BNP secretion occurs independently of PCWP in a setting of increasing intravascular volume and consciousness/sympathetic tone.

Hypothermic circulatory arrest using antegrade cerebral perfusion is safe for elective aortic arch surgery.

BACKGROUND: We hypothesized that hypothermic circulatory arrest (HCA) can be performed with a low operative risk and does not add to the morbidity in elective procedures. METHODS: A total of 178 patients with a mean (± SD) age of 62 (± 10) years underwent HCA for elective aortic surgery from April 2008 to September 2011. Pre- and postoperative clinical data were collected prospectively. RESULTS: Hemiarch replacement was performed in 97% patients. Mean logistic Euroscore I was 17% (± 15). HCA was performed at 26°C bilateral tympanic temperature. Mean HCA duration was 17 (±) min. Mean cross-clamp time was 106 (± 39) min. Overall 30-day mortality was 2% and stroke occurred in 4% of patients. Overall 6-month survival was 96%. Cox regression analysis for 6-month survival revealed four variables with significant influence: the logistic Euroscore I (p = 0.008), age (p = 0.04), cross-clamp time (p = 0.008), and reoperation for bleeding complications (p = 0.04). CONCLUSIONS: HCA with open distal anastomosis for elective aortic repair can be performed with low operative mortality, even in the elderly, and seems not to add to the morbidity of the procedure.

Prognostic value of Sequential Organ Failure Assessment and Simplified Acute Physiology II Score compared with trauma scores in the outcome of multiple-trauma patients.

BACKGROUND: Prospective data regarding the prognostic value of the Sequential Organ Failure Assessment (SOFA) score in comparison with the Simplified Acute Physiology Score (SAPS II) and trauma scores on the outcome of multiple-trauma patients are lacking. METHODS: Single-center evaluation (n = 237, Injury Severity Score [ISS] >16; mean ISS = 29). Uni- and multivariate analysis of SAPS II, SOFA, revised trauma, polytrauma, and trauma and ISS scores (TRISS) was performed. RESULTS: The 30-day mortality was 22.8% (n = 54). SOFA day 1 was significantly higher in nonsurvivors compared with survivors (P < .001) and correlated well with the length of intensive care unit stay (r = .50, P < .001). Logistic regression revealed SAPS II to have the best predictive value of 30-day mortality (area under the receiver operating characteristic = .86 +/- .03). The SOFA score significantly added prognostic information with regard to mortality to both SAPS II and TRISS. CONCLUSIONS: The combination of critically ill and trauma scores may increase the accuracy of mortality prediction in multiple-trauma patients.

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial.

OBJECTIVE: Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery. DESIGN: : Double-blind, randomized, placebo-controlled trial. SETTING: One Swiss University Hospital. PATIENTS: One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTION: Patients were randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day. MEASUREMENTS AND MAIN RESULTS: The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively. Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests, and the use of a rescue treatment consisting of haloperidol and/or lorazepam in patients with delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine groups, respectively. CONCLUSION: This negative or, because of methodologic issues, possibly failed trial does not support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass.

Cerebral perfusion in sepsis-associated delirium.

INTRODUCTION: The pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium. METHODS: We investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100beta, and cortisol were measured during each data acquisition. RESULTS: Data from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100beta (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010). CONCLUSION: In this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100beta and cortisol in the diagnosis of sepsis-associated delirium are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00410111.

Measurement of serum free cortisol shows discordant responsivity to stress and dynamic evaluation.

CONTEXT: Routinely available assays of adrenal function measure serum total cortisol (TC) and not the biologically active free cortisol (FC). However, there are few data on FC levels during surgical stress and in response to standard pharmacological tests. OBJECTIVE: Our objective was to evaluate TC and FC levels in different states of physical stress. DESIGN AND SETTING: We conducted a prospective observational study in a university hospital. PARTICIPANTS AND MAIN OUTCOME MEASURES: We measured TC and FC levels in 64 patients: group A, 17 healthy controls without stress; group B, 23 medical patients with moderate stress; and group C, 24 surgical patients undergoing coronary bypass grafting. Cortisol levels in group C were measured basally and at several time points thereafter and were compared with responsivity to a pharmacological dose of ACTH. FC was measured using equilibrium dialysis. RESULTS: In group C patients after extubation, the relative increase above basal FC was higher than the increase in TC levels (399 +/- 266 vs. 247 +/- 132% of initial values, respectively; mean +/- sd; P = 0.02) and then fell more markedly, FC levels falling to 67 +/- 49% and TC levels to 79 +/- 36% (P = 0.04). After ACTH stimulation, TC levels increased to 680 +/- 168 nmol/liter, which was similar to the increase with major stress (811 +/- 268 nmol/liter). In contrast, FC levels increased to 55 +/- 16 nmol/liter after ACTH stimulation but significantly greater with surgical stress to 108 +/- 56 nmol/liter (P < 0.001). CONCLUSION: The more pronounced increase in FC seen during stress as compared with the ACTH test suggests that this test does not adequately anticipate the FC levels needed during severe stress.

The impact of postoperative nasal packing on sleep-disordered breathing and nocturnal oxygen saturation in patients with obstructive sleep apnea syndrome.

Nasal septum surgery is frequently performed to establish a functional nasal airway. In these patients obstructive sleep apnea syndrome (OSAS) is frequently present. Although patients with OSAS are at increased risk for hypoxemia, the impact of postoperative nasal packing (PNP) on sleep-disordered breathing and oxygen desaturations in patients with OSAS is unknown. We consecutively investigated 40 patients undergoing endonasal surgery receiving PNP. Fifteen of these patients had previously diagnosed OSAS (Group 2) and 25 did not (Group 1). In the control group, 12 healthy patients underwent elective ear or neck surgery without PNP. During the preoperative and postoperative nights, we continuously measured oronasal flow, thoracoabdominal movements, and oxygen saturation. We calculated the apnea-hypopnea index (AHI) and the oxygen-desaturation index (ODI). Compared with the preoperative values, after the operation, neither AHI nor ODI changed in the control group. In contrast, in Group 1, AHI (from 11 [5-19] to 37 [22-49]) and ODI (from 4 [2-8] to 13 [6-21]) significantly increased (P < 0.05), whereas in Group 2, only AHI significantly increased (from 14 [10-21] to 39 [26-50]); ODI remained similar (13 [8-27] versus 11 [4-37]). Because ODI did not increase in patients with OSAS and PNP who received postoperative oxygen overnight, postoperative intensive care monitoring might not be necessary on a routine basis for all patients with PNP and OSAS.

Management of acute respiratory distress syndrome using pumpless extracorporeal lung assist.

PURPOSE: To describe the use of a pumpless extracorporeal lung assist device in the treatment of severe acute respiratory distress syndrome (ARDS). CLINICAL FEATURES: A 15-yr-old girl developed severe post-traumatic ARDS. After all conventional treatment strategies failed, we inserted a pumpless extracorporeal lung assist device. This device consists of an arterial cannula inserted into the femoral artery, and a membrane oxygenator with a venous cannula that returns the oxygenated blood back to the patient's femoral vein. Since the driving force is the patient's blood pressure, a roller pump with its negative side effects is not needed. The device allowed removal of excessive PaCO(2) and, by applying minimal ventilation, minimization of further ventilator-induced lung injury. The pumpless extracorporeal lung assist device remained in situ for ten days without any adverse side effect. During this time, the lung recovered such that mechanical ventilation could be reinstalled cautiously. The device was then removed and, after a prolonged period of intensive care, the patient recovered without any sequelae. CONCLUSION: In this case of a severely damaged lung, an arteriovenous pumpless extracorporeal lung assist was a helpful device to remove elevated CO(2) and reduce mechanical stress by applying minimal ventilation. This device is simple to operate and has the potential of being used routinely in the treatment of severe ARDS.