Factors influencing the end-of-life decisionmaking process about care in hospitalized patients.

The quality of end-of-life care of hospitalized patients is an important topic, but so far little explored in the Czech Republic. The aim of this study was to map the factors influencing the end-of-life care decision-making process in selected Czech hospitals and to describe it based on data from medical records and from the perspective of a doctor. The research included data obtained from the medical records of 240 deceased patients (mean age 76.9 years, 41.6% women). The research sample of medical doctors who commented on the decision-making about end-of-life care for these patients consisted of 369 physicians (mean age 35.9 years, 61% women). The results pointed to persistent deficiencies in the written recording of the care goals, prognosis, and possible decision to limit care. Medical doctors limit health care primarily based on consensus among physicians, the patient is usually not invited to the decision-making process. Patient preferences for the end-of-life period are in most cases not ascertained or this question is postponed. The institute of a previously stated wish did not appear in the examined group at all. It can be concluded that decisions about end-of-life care usually take place without knowledge of patients' values ​​and preferences. The results indicate the need to improve the training of doctors and medical students, which should, in addition to building professional competencies, include training in effective communication with patients at the end of life.

Simvastatin impairs the induction of pulmonary fibrosis caused by a western style diet: a preliminary study.

The role of an atherogenic diet in causing pulmonary fibrosis has received little attention and simvastatin has been shown to reduce pulmonary fibrosis in animal models. To determine if an atherogenic diet can induce pulmonary fibrosis and whether simvastatin treatment is beneficial by up-regulating heat shock protein 70 and 90. New Zealand white rabbits (n = 15) were divided: Group 1 (control); Group 2 (MC) received a normal rabbit diet with 1% methionine plus 0.5% cholesterol (atherogenic diet). Group 3 received the same diet as the MC group plus 5 mg/kg/day simvastatin orally (MCS). After 4 weeks, the lungs were collected and analysed. Picrosirus red staining of lung interstitial collagen content showed that the atherogenic diet increased fibrosis 2.9-fold (P < 0.05), bronchiole adventitial collagen was increased 2.3-fold (P < 0.05) and bronchiole epithelium was increased 34-fold (P < 0.05), and simvastatin treatment severely reduced this effect (P < 0.05). Western blot analysis showed that the atherogenic diet significantly reduced lung Hsp70 protein by 22% (P < 0.05) and Hsp90 protein by 18% (P < 0.05) and simvastatin treatment did not affect this result. However, aortic hyper-responsiveness to vasoconstrictors (angiotensin II and phenylephrine) were markedly reduced by simvastatin treatment. We report that an atherogenic diet stimulates pulmonary fibrosis and reduces lung Hsp70/Hsp90 protein concentration. Simvastatin impairs this by mechanisms unrelated to Hsp70/Hsp90, but possibly a reduction in angiotensin II receptor or alpha adrenergic receptor pathways. These results could have implications in idiopathic pulmonary fibrosis.

Regional differences of vasodilatation and vasomotion response to local heating in human cutaneous microcirculation.

BACKGROUND: The aim of this study was to evaluate the vasodilatation and vasomotion response to local heating in the cutaneous microcirculation of the ankle, dorsum of foot and forearm. Recently, it has been suggested that this response differs between the forearm and the leg. PROBANDS AND METHODS: Twenty-nine young healthy adults were recruited. They underwent measurement by laser Doppler flowmetry (LDF) in three sites of the body (ankle, dorsum of foot, forearm). Percentage change of the median flow of the skin before and after provocation and normalised perfusion flow to maximal dilation (cutaneous vascular conductance--CVC % Max) during short provocation test were monitored. Spectral analysis of laser Doppler flowmetry signals was performed using the fast Fourier transform algorithm. RESULTS: Significant differences were found in CVC % Max between ankle/dorsum (45.18±6.38% Max vs. 51.24±6.87% Max, respectively; p<0.05) and between ankle/forearm (45.18±6.38% Max vs. 54.49±5.37% Max, respectively; p<0.05). Percentage change of flux after provocation has revealed significant differences between ankle/dorsum (394.1±204.5% vs. 577.4±273.5%, respectively; p<0.05) and ankle/forearm (394.1±204.5% vs. 637.1±324.7%, respectively; p<0.05). Total spectral activity of vasomotion has differed between ankle/dorsum and ankle/forearm: 69.59 [49.58-96.04] vs. 93.01 [73.15-121.8] (p<0.05) and 69.59 [49.58-96.04] vs. 107.5 [80.55-155.8] (p<0.05), respectively. CONCLUSIONS: Cutaneous microcirculation exhibits regional differences. Significant variability of function between ankle and dorsum of foot suggests that leg microcirculation is not uniform.

The impact of sedation on pulse pressure variation.

OBJECTIVE: Pulse pressure variations (PPV) are mainly influenced by ventilation. The impact of sedation on PPV is not known. The aim of the study was to test the influence of sedation on pulse pressure variation in mechanically ventilated critically ill patients and to compare PPV in critically ill and brain dead patients. Beside the absolute value of PPV, the adjusted values of pulse pressure were used to eliminate influence of ventilation. DESIGN AND INTERVENTION: Mechanically ventilated patients received four different breath frequencies. At each frequency airway pressure was adjusted to keep the end-tidal CO2 stable. In critically ill patients the frequencies were applied at basal (bispectral index - BIS median 38) and deeper sedation (BIS 29). MAIN OUTCOME MEASURES: Simultaneous haemodynamic and respiratory data including oesophageal pressure were recorded, adjusted PPV were calculated as PPV/VT, PPV/dPair, PPV/dPes where VT is tidal volume, dPair and dPes are airway and oesophageal driving pressures. SETTING: University Hospital, ICU. PARTICIPANTS: 30 critically ill and 23 patients with a diagnosis of brain death. RESULTS: The pulse pressure variation did not change significantly during deep sedation compared to basal sedation (median 10.3 vs 10.9%) whereas PPV/dPair increased from 0.7 to 0.8%/cmH2O and PPV/dPes from 1.9%/cmH2O to 2.4%/cmH2O (p=0.04). Patients with a diagnosis of brain death had higher PPV and adjusted PPV than critically ill patients. CONCLUSION: Deeper sedation increases values of adjusted pulse pressure variation.

Intravenous insulin therapy during lung resection does not affect lung function or surfactant proteins.

BACKGROUND: The surgical resection of lung disrupts glucose homeostasis and causes hyperglycemia, as in any other major surgery or critical illness. We performed a prospective study where we carefully lowered hyperglycemia by insulin administration during the surgery, and for the first time we monitored immediate insulin effects on lung physiology and gene transcription. METHODS: The levels of blood gases (pH, pCO2, pO2, HCO3-, HCO3- std, base excess, FiO2, and pO2/FiO2) were measured at the beginning of surgery, at the end of surgery, and two hours after. Samples of healthy lung tissue surrounding the tumour were obtained during the surgery, anonymized and sent for subsequent blinded qPCR analysis (mRNA levels of surfactant proteins A1, A2, B, C and D were measured). This study was done on a cohort of 64 patients who underwent lung resection. Patients were randomly divided, and half of them received insulin treatment during the surgery. RESULTS: We demonstrated for the first time that insulin administered intravenously during lung resection does not affect levels of blood gases. Furthermore, it does not induce immediate changes in the expression of surfactant proteins. CONCLUSION: According to our observations, short insulin treatment applied intravenously during resection does not affect the quality of breathing.

Temperature corrected thromboelastography in hypothermia: is it necessary?

CONTEXT: Hypothermia is known to influence thromboelastography (TEG). TEG reproducibility is generally low. OBJECTIVE: The aim of this study was to evaluate the rationale of TEG temperature adjustment in patients during hypothermia. We hypothesised that temperature adjustment would not be important because of low TEG reproducibility. DESIGN: Prospective observational study. SETTING: Single-centre, secondary care study performed 01/2009 to 07/2010. PATIENTS: Survivors of cardiopulmonary resuscitation in whom therapeutic hypothermia (32 to 34°C) was indicated for 24 h were recruited to the study which lasted 36 h. Four hundred samples from 30 patients (22 men and eight women) were obtained. No specific exclusion criteria were defined. MAIN OUTCOME MEASURES: Temperature adjusted and non-adjusted Kaolin-Heparinase and Rapid-TEG were done at 12-h intervals during the first 36 h. RESULTS: Bland-Altman plots were used for analysis. During hypothermia, the bias of adjusted measurements was greater in clot formation variables for both Kaolin-Heparinase-TEG (from -15 to -19%) and Rapid-TEG (-9 to -25%) compared to normothermia (from -3 to 3% for Kaolin-Heparinase-TEG and -10 to 2% for Rapid-TEG). Bias of clot strength variables was not influenced by temperature adjustment (median -1%). The 95% limits of agreement were wide for clot formation variables and independent of temperature. In Kaolin-Heparinase-TEG (R -42 to 40% normothermia, -47 to 18% hypothermia) and in Rapid-TEG (R -117 to 97% normothermia, -114 to 95% hypothermia). Limits of agreement of clot strength variables were narrower and independent of temperature in Kaolin-Heparinase-TEG (MA -16 to 13% normothermia, -9 to 10% hypothermia) and also in Rapid-TEG (MA -27 to 24% normothermia, -18 to 20% hypothermia). CONCLUSION: Although TEG analysis with temperature adjusted to the in-vivo value during hypothermia yields results with small systematic bias, the importance of temperature adjustment in clinical routine is low because of the precision limits of TEG measurement itself. Therefore, we see no need to perform TEG analysis at the in-vivo temperature.

Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU.

BACKGROUND: Novel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection. METHODS: Design: Prospective, multi-centre, double-blind, randomised, controlled trial (RCT). PARTICIPANTS: Adult (> 18 years) within 24 h of admission to the intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for ≥ 1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, and pregnancy. INTERVENTIONS: Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800 mg orally in two doses followed by 400 mg daily in two doses and azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or hydroxychloroquine + placebo (HC group) or placebo + placebo (C-group) in addition to the best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. SECONDARY OUTCOMES: The percentage of patients who were prevented from needing intubation until day 14, ICU length of stay, and mortality (in hospital) at day 28 and 90. DISCUSSION: Although both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggests their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patient-centred outcomes, such as mechanical ventilation-free survival. TRIAL REGISTRATION: Clinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).

Postintubation tracheal rupture: case report.

Tracheobronchial rupture after tracheal intubation has been infrequently reported. Successful diagnosis often requires a high level of suspicion. A laceration of the distal membranous trachea usually has been repaired through a right thoracotomy.

Respiratory induced heart rate variability during slow mechanical ventilation : Marker to exclude brain death patients.

BACKGROUND: Respiratory induced heart rate variability (rHRV) was analysed in mechanically ventilated patients during two levels of sedation and brain death. Our aim was to determine whether rHRV can distinguish between different levels of sedation and especially between brain death and sedated patients. METHODS: In this study 30 critically ill and 23 brain death patients were included and four respiratory rates of 15, 12, 8 and 6 breaths per minute, each lasting 5 min were used. Two sedation levels, basal and deep, were performed in the critically ill patients. Heart rate and blood pressure changes induced by ventilation were subsequently detected and analysed. RESULTS: Significant differences were found in rHRV and rHRV adjusted for tidal volume (rHRV/VT) between critically ill and brain death patients during slow breathing at 6 or 8 breaths per minute. The rHRV at 6 breaths per minute was below 15 ms in all brain death subjects except one. The rHRV/VT was lower than 25 ms/l at both 6 and 8 breaths per minute in all brain death patients and simultaneously at 75% of non-brain death patients was higher (specificity 1, sensitivity 0.24). Differences in rHRV and rHRV/VTs between basal and deep sedation were not significant. CONCLUSIONS: The main clinical benefit of the study is the finding that rHRV and rHRV/VT during 6 and 8 breaths per minute can differentiate between critically ill and brain death patients. An rHRV/VT exceeding 25 ms/l reliably excludes brain death.

Differential effects of insulin and dexamethasone on pulmonary surfactant-associated genes and proteins in A549 and H441 cells and lung tissue.

In this study, the effects of insulin and dexamethasone on the expression and mRNA transcription of 4 pulmonary surfactant-associated proteins [surfactant protein (SFTP)A, SFTPB, SFTPC and SFTPD] were examined. The commercially available cell lines, A549 and H441, were used as acceptable models of lung surfactant-producing cells. Subsequently, the effects of insulin on the expression of surfactant-associated proteins were examined in patients with lung adenocarcinoma during lung resection. Our results demonstrated the inhibitory effects of insulin on the transcription of the SFTPB, SFTPC and SFTPD genes in H441 cells and the SFTPB gene in A549 cells. Treatment with insulin significantly decreased the protein expression of SFTPA1 and SFTPA2 in the H441 cells and that of proSFTPB in the A549 cells. Dexamethasone promoted the transcription of the SFTPB, SFTPC and SFTPD genes in the A549 and H441 cells and reduced the transcription of the SFTPA1 and SFTPA2 genes in the H441 cells (SFTPA mRNA expression was not detected in A549 cells). Furthermore, we demonstrated that the mRNA levels of the selected genes were significantly lower in the cell lines compared to the lung tissue. A549 and H441 cells represent similar cell types. Yet, in our experiments, these cells reacted differently to insulin and/or dexamethasone treatment, and the mRNA levels of their main protein products, surfactant-associated proteins, were significantly lower than those in real tissue. Therefore, the results obtained in this study challenge the suitability of A549 and H441 cells as models of type II pneumocytes and Clara cells, respectively. However, we successfully demonstrate the possibility of studying the effects of insulin on pulmonary surfactant-associated genes and proteins in patients with lung adenocarcinoma.