When Palliative Care May Be the Only Option in the Management of Severe Burns: A Case Report Written With the Help of ChatGPT.

We present a case of 100% third-degree burns. The patient received full resuscitative measures, but the family was prepared for a poor outcome based on the severe extent of the injuries. After several days of treatment, it became apparent that the patient indeed could not survive the injuries and palliative care was instituted, including mechanical ventilation, fluid therapy, and analgesia. Surgery was not possible without causing major disfigurement, including enucleation of both eyes and amputation of all limbs.

Variations in end-of-life care practices in older critically ill patients with COVID-19 in Europe.

BACKGROUND: Previous studies reported regional differences in end-of-life care (EoLC) for critically ill patients in Europe. OBJECTIVES: The purpose of this post-hoc analysis of the prospective multicentre COVIP study was to investigate variations in EoLC practices among older patients in intensive care units during the coronavirus disease 2019 pandemic. METHODS: A total of 3105 critically ill patients aged 70 years and older were enrolled in this study (Central Europe: n = 1573; Northern Europe: n = 821; Southern Europe: n = 711). Generalised estimation equations were used to calculate adjusted odds ratios (aORs) to population averages. Data were adjusted for patient-specific variables (demographic, disease-specific) and health economic data (gross domestic product, health expenditure per capita). The primary outcome was any treatment limitation, and 90-day mortality was a secondary outcome. RESULTS: The frequency of the primary endpoint (treatment limitation) was highest in Northern Europe (48%), intermediate in Central Europe (39%) and lowest in Southern Europe (24%). The likelihood for treatment limitations was lower in Southern than in Central Europe (aOR 0.39; 95% confidence interval [CI] 0.21-0.73; p = 0.004), even after multivariable adjustment, whereas no statistically significant differences were observed between Northern and Central Europe (aOR 0.57; 95%CI 0.27-1.22; p = 0.15). After multivariable adjustment, no statistically relevant mortality differences were found between Northern and Central Europe (aOR 1.29; 95%CI 0.80-2.09; p = 0.30) or between Southern and Central Europe (aOR 1.07; 95%CI 0.66-1.73; p = 0.78). CONCLUSION: This study shows a north-to-south gradient in rates of treatment limitation in Europe, highlighting the heterogeneity of EoLC practices across countries. However, mortality rates were not affected by these results.

Disease-Course Adapting Machine Learning Prognostication Models in Elderly Patients Critically Ill With COVID-19: Multicenter Cohort Study With External Validation.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 is challenging health care systems globally. The disease disproportionately affects the elderly population, both in terms of disease severity and mortality risk. OBJECTIVE: The aim of this study was to evaluate machine learning-based prognostication models for critically ill elderly COVID-19 patients, which dynamically incorporated multifaceted clinical information on evolution of the disease. METHODS: This multicenter cohort study (COVIP study) obtained patient data from 151 intensive care units (ICUs) from 26 countries. Different models based on the Sequential Organ Failure Assessment (SOFA) score, logistic regression (LR), random forest (RF), and extreme gradient boosting (XGB) were derived as baseline models that included admission variables only. We subsequently included clinical events and time-to-event as additional variables to derive the final models using the same algorithms and compared their performance with that of the baseline group. Furthermore, we derived baseline and final models on a European patient cohort, which were externally validated on a non-European cohort that included Asian, African, and US patients. RESULTS: In total, 1432 elderly (≥70 years old) COVID-19-positive patients admitted to an ICU were included for analysis. Of these, 809 (56.49%) patients survived up to 30 days after admission. The average length of stay was 21.6 (SD 18.2) days. Final models that incorporated clinical events and time-to-event information provided superior performance (area under the receiver operating characteristic curve of 0.81; 95% CI 0.804-0.811), with respect to both the baseline models that used admission variables only and conventional ICU prediction models (SOFA score, P<.001). The average precision increased from 0.65 (95% CI 0.650-0.655) to 0.77 (95% CI 0.759-0.770). CONCLUSIONS: Integrating important clinical events and time-to-event information led to a superior accuracy of 30-day mortality prediction compared with models based on the admission information and conventional ICU prediction models. This study shows that machine-learning models provide additional information and may support complex decision-making in critically ill elderly COVID-19 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04321265; https://clinicaltrials.gov/ct2/show/NCT04321265.

A new multi-national network studying Very old Intensive care Patients (VIPs).

In Europe there are increasing numbers of old (more than 65 years old) and very old (more than 80 years old) patients (very old intensive care patients - VIPs) (Figure 1). In addition to combinations of chronic conditions (multi-morbidity), there are geriatric disabilities and functional limitations, with a profound impact on management in the ICU and afterwards [1].

Attitudes of legal guardians in the ICU - a qualitative report.

UNLABELLED: Decision-making in intensive care units (ICUs) is often made by surrogates, since patients are unconscious or incompetent. In Israel, Legal Guardians (LGs), appointed by the court, are required to make these decisions. OBJECTIVE: To qualitatively assess the attitudes of LGs required to make decisions on behalf of their relatives. RESEARCH DESIGN: Demographic and semi-structured questionnaires were used to assess the attitudes of LGs regarding difficulties, positive aspects and areas for improvement with regard to surrogate decision-making. The study sampled sixty-four LGs in two large Israeli hospitals. After reading and analysing the responses provided by the LGs, the authors categorised the pertinent topics raised using a thematic analysis. RESULTS: Themes were: bureaucratic and legal issues, unclear or unknown patient preferences and fear of outcomes. Family and medical staff support was stated as the most beneficial. Suggestions for improvement included alleviation of bureaucracy and improved communication with the medical staff. CONCLUSIONS: The importance of communication and bureaucratic difficulties, making the best decision for the patient and uncertainty regarding decision outcomes were found to be important issue for the LGs. The healthcare team should try and alleviate some of these burdens, mostly by improving communication with relatives, stressing and educating the importance of advance directives. Reporting the problems found in the decision making process of LGs to the legislators in order to revise and simplify the current legal requirements is advised.

Intensive care unit occupancy after introduction of the emergency department 4-hour discharge rule at a tertiary referral hospital in Western Australia.

BACKGROUND: The 4-hour rule has been introduced in Western Australia, requiring that emergency department (ED) patients be admitted to hospital or discharged from the ED within 4 hours of presentation. We hypothesised that this rule might have been associated with changes in medical emergency team (MET) calls and intensive care unit exit bed block. METHODS: Hospital databases were examined to determine compliance with the 4-hour rule, the effect on ICU exit bed block, and the number of MET calls, in 2008 (before introduction of the 4-hour rule) and 2011 (after introduction of the 4-hour rule). We also measured background ICU and hospital activity in 2008 and 2011. RESULTS: Monthly compliance with the 4-hour rule ranged from 35%-46% in 2008 to 64%-75% in 2011 (P < 0.0001). There was a marked increase in bed block days for patients in the ICU between 2008 (before introduction of the 4-hour rule) and 2011 (after introduction of the 4-hour rule) (P = 0.05). The increase in ICU bed block-days could not be explained by a difference in ICU occupancy, as there was a reduction in ICU bed-days between 2008 and 2011 (P = 0.014). There was a reduction in hospital mortality rate between 2008 and 2011 (P < 0.001). There was no significant increase in the number of MET calls from 2008 to 2011 (P = 0.221). Hospital activity (separations) increased from 2008 to 2011 (P < 0.0001). DISCUSSION: The introduction of the 4-hour rule was associated with increased exit block from the ICU, but not with increased MET calls to attend to unstable or deteriorating ward patients. Introduction of the 4-hour rule was associated with a small reduction in hospital mortality.

Matching positive end-expiratory pressure to intra-abdominal pressure improves oxygenation in a porcine sick lung model of intra-abdominal hypertension.

INTRODUCTION: Intra-abdominal hypertension (IAH) causes atelectasis, reduces lung volumes and increases respiratory system elastance. Positive end-expiratory pressure (PEEP) in the setting of IAH and healthy lungs improves lung volumes but not oxygenation. However, critically ill patients with IAH often suffer from acute lung injury (ALI). This study, therefore, examined the respiratory and cardiac effects of positive end-expiratory pressure in an animal model of IAH, with sick lungs. METHODS: Nine pigs were anesthetized and ventilated (48 +/- 6 kg). Lung injury was induced with oleic acid. Three levels of intra-abdominal pressure (baseline, 18, and 22 mmHg) were randomly generated. At each level of intra-abdominal pressure, three levels of PEEP were randomly applied: baseline (5 cmH2O), moderate (0.5 × intra-abdominal pressure), and high (1.0 × intra-abdominal pressure). We measured end-expiratory lung volumes, arterial oxygen levels, respiratory mechanics, and cardiac output 10 minutes after each new IAP and PEEP setting. RESULTS: At baseline PEEP, IAH (22 mmHg) decreased oxygen levels (-55%, P <0.001) and end-expiratory lung volumes (-45%, P = 0.007). At IAP of 22 mmHg, moderate and high PEEP increased oxygen levels (+60%, P = 0.04 and +162%, P <0.001) and end-expiratory lung volume (+44%, P = 0.02 and +279%, P <0.001) and high PEEP reduced cardiac output (-30%, P = 0.04). Shunt and dead-space fraction inversely correlated with oxygen levels and end-expiratory lung volumes. In the presence of IAH, lung, chest wall and respiratory system elastance increased. Subsequently, PEEP decreased respiratory system elastance by decreasing chest wall elastance. CONCLUSIONS: In a porcine sick lung model of IAH, PEEP matched to intra-abdominal pressure led to increased lung volumes and oxygenation and decreased chest wall elastance shunt and dead-space fraction. High PEEP decreased cardiac output. The study shows that lung injury influences the effects of IAH and PEEP on oxygenation and respiratory mechanics. Our findings support the application of PEEP in the setting of acute lung injury and IAH.

Matching positive end-expiratory pressure to intra-abdominal pressure prevents end-expiratory lung volume decline in a pig model of intra-abdominal hypertension.

OBJECTIVE: Intra-abdominal hypertension is common in critically ill patients and is associated with increased morbidity and mortality. In a previous experimental study, positive end-expiratory pressures of up to 15 cm H2O did not prevent end-expiratory lung volume decline caused by intra-abdominal hypertension. Therefore, we examined the effect of matching positive end-expiratory pressure to the intra-abdominal pressure on cardio-respiratory parameters. DESIGN: Experimental pig model of intra-abdominal hypertension. SETTING: Large animal facility, University of Western Australia. SUBJECTS: Nine anesthetized, nonparalyzed, and ventilated pigs (48 ± 7 kg). INTERVENTIONS: Four levels of intra-abdominal pressure (baseline, 12, 18, and 22 mm Hg) were generated in a randomized order by inflating an intra-abdominal balloon. At each level of intra-abdominal pressure, three levels of positive end-expiratory pressure were randomly applied with varying degrees of matching the corresponding intra-abdominal pressure: baseline positive end-expiratory pressure (= 5 cm H2O), moderate positive end-expiratory pressure (= half intra-abdominal pressure in cm H2O + 5 cm H2O), and high positive end-expiratory pressure (= intra-abdominal pressure in cm H2O). MEASUREMENTS: We measured end-expiratory lung volume, arterial oxygen levels, respiratory mechanics, and cardiac output 5 mins after each new intra-abdominal pressure and positive end-expiratory pressure setting. MAIN RESULTS: Intra-abdominal hypertension decreased end-expiratory lung volume and PaO2 (-49% [p < .001] and -8% [p < .05], respectively, at 22 mm Hg intra-abdominal pressure compared with baseline intra-abdominal pressure) but did not change cardiac output (p = .5). At each level of intra-abdominal pressure, moderate positive end-expiratory pressure increased end-expiratory lung volume (+119% [p < .001] at 22 mm Hg intra-abdominal pressure compared with 5 cm H2O positive end-expiratory pressure) while minimally decreasing cardiac output (-8%, p < .05). High positive end-expiratory pressure further increased end-expiratory lung volume (+233% [p < .001] at 22 mm Hg intra-abdominal pressure compared with 5 cm H2O positive end-expiratory pressure) but led to a greater decrease in cardiac output (-26%, p < .05). Neither moderate nor high positive end-expiratory pressure improved PaO2 (p = .7). Intra-abdominal hypertension decreased end-expiratory transpulmonary pressure but did not alter end-inspiratory transpulmonary pressure. Intra-abdominal hypertension decreased total respiratory compliance through a decrease in chest wall compliance. Positive end-expiratory pressure decreased the respiratory compliance by reducing lung compliance. CONCLUSIONS: In a pig model of intra-abdominal hypertension, positive end-expiratory pressure matched to intra-abdominal pressure led to a preservation of end-expiratory lung volume, but did not improve arterial oxygen tension and caused a reduction in cardiac output. Therefore, we do not recommend routine application of positive end-expiratory pressure matched to intra-abdominal pressure to prevent intra-abdominal pressure-induced end-expiratory lung volume decline in healthy lungs.

The role of femoral venous pressure and femoral venous oxygen saturation in the setting of intra-abdominal hypertension: a pig model.

Femoral venous access is frequently used in critically ill patients. Because raised intra-abdominal pressure (IAP) is also frequently found in this group of patients, we examined the impact of IAP and positive end-expiratory pressure (PEEP) on femoral venous pressure (FVP) and femoral venous oxygen saturation (Sfvo2) in an animal model. Thirteen adult pigs received standardized anesthesia and ventilation. Randomized levels of IAP (3 [baseline], 18, and 26 mmHg) were applied, with levels of PEEP (5, 8, 12, and 15 cmH2O) applied randomly at each IAP level. We measured bladder pressure (IAP), superior vena cava pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, FVP, mixed venous oxygen saturation (Svo2), and Sfvo2. We found that FVP correlated well with IAP (FVP = 4.1 + [0.12 × PEEP] + [1.00 × IAP]; R = 0.89, P < 0.001) with a moderate bias and precision of 5.0 and 3.8 mmHg, respectively. Because the level of agreement did not meet the recommendations of the World Society of Abdominal Compartment Syndrome, FVP cannot currently be recommended to measure IAP, and further clinical trials are warranted. However, a raised FVP should prompt the measurement of the bladder pressure. Femoral venous oxygen saturation did correlate neither with Svo2 nor with abdominal perfusion pressure. Therefore, Sfvo2 is of no clinical use in the setting of raised IAP.

Commonly applied positive end-expiratory pressures do not prevent functional residual capacity decline in the setting of intra-abdominal hypertension: a pig model.

INTRODUCTION: Intra-abdominal hypertension is common in critically ill patients and is associated with increased morbidity and mortality. The optimal ventilation strategy remains unclear in these patients. We examined the effect of positive end-expiratory pressures (PEEP) on functional residual capacity (FRC) and oxygen delivery in a pig model of intra-abdominal hypertension. METHODS: Thirteen adult pigs received standardised anaesthesia and ventilation. We randomised three levels of intra-abdominal pressure (3 mmHg (baseline), 18 mmHg, and 26 mmHg) and four commonly applied levels of PEEP (5, 8, 12 and 15 cmH2O). Intra-abdominal pressures were generated by inflating an intra-abdominal balloon. We measured intra-abdominal (bladder) pressure, functional residual capacity, cardiac output, haemoglobin and oxygen saturation, and calculated oxygen delivery. RESULTS: Raised intra-abdominal pressure decreased FRC but did not change cardiac output. PEEP increased FRC at baseline intra-abdominal pressure. The decline in FRC with raised intra-abdominal pressure was partly reversed by PEEP at 18 mmHg intra-abdominal pressure and not at all at 26 mmHg intra-abdominal pressure. PEEP significantly decreased cardiac output and oxygen delivery at baseline and at 26 mmHg intra-abdominal pressure but not at 18 mmHg intra-abdominal pressure. CONCLUSIONS: In a pig model of intra-abdominal hypertension, PEEP up to 15 cmH2O did not prevent the FRC decline caused by intra-abdominal hypertension and was associated with reduced oxygen delivery as a consequence of reduced cardiac output. This implies that PEEP levels inferior to the corresponding intra-abdominal pressures cannot be recommended to prevent FRC decline in the setting of intra-abdominal hypertension.

Diethylenetriamine nitric oxide adduct relaxes precontracted mouse tracheal smooth muscle.

1. Inhaled diethylenetriamine nitric oxide adduct (DETA/NO) has been shown to be a selective pulmonary vasodilator in animal and human studies. The aims of the present study were to investigate the effect of DETA/NO on mouse precontracted isolated tracheal smooth muscle preparations and to determine the active component of this compound. 2. Mouse isolated tracheal smooth muscle rings were precontracted with carbachol (10-7 mol/L). Changes in isometric tension were recorded after cumulative addition of DETA (30-300 micromol/L; n = 6), DETA/NO (30-300 micromol/L; n = 9) or diluent control (n = 3). In addition, some preparations (n = 5) were pretreated with the soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]-oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; 30 micromol/L) before precontraction and exposure to DETA/NO. 3. Addition of DETA/NO caused a concentration-dependent relaxation of tracheal smooth muscle at 100 and 300 micromol/L, with an EC25%R of 109 micromol/L (95% confidence interval 72.6-164 micromol/L). The nucleophile amine carrier DETA had no effect on isometric tension. However, the relaxant effect of DETA/NO was completely abolished by pretreatment with ODQ. 4. We conclude that DETA/NO induces a concentration-dependent relaxation of mouse carbachol-contracted isolated tracheal smooth muscle that is mediated by NO released from DETA/NO via the activation of sGC.

The safety of aerosolized diethylenetriamine nitric oxide adduct after single-dose administration to anesthetized piglets and multiple-dose administration to conscious rats.

Diethylenetriamine nitric oxide adduct (DETA/NO) is a slow-release NO donor. It has been shown to be a selective pulmonary vasodilator in acute pulmonary hypertension. However, its potential toxicity after inhalation is unknown. This study investigated the potential toxicity of aerosolized DETA/NO after single- and multiple-dose exposure in animals. In the first part of the study, a single dose of DETA/NO (60 micromol) or placebo was aerosolized into the lungs of anesthetized piglets. Arterial methemoglobin and serum nitrite (NO2-) concentrations were measured after exposure. In the second part of the study, rats were exposed to aerosolized DETA/NO (60 micromol) or placebo for 7 days, and animals were euthanized 1, 3, 7, and 14 days after the first exposure. Serum NO2- and plasma surfactant protein B (SP-B) concentrations were measured. In both studies, acute lung inflammation was evaluated histopathologically (polymorphonuclear leucocytes (PMN) infiltration) and by measuring lung wet to dry weight ratio (LWDR). The tracheas of rats, which had the highest exposure, were further examined for ultrastructural changes using electron microscopy. In both rats and pigs, serum NO2- concentrations were elevated in all the DETA/NO-treated animals, indicating significant exposure to DETA/NO. Arterial methemoglobin was not increased by DETA/NO treatment. In the rats, plasma SP-B was not elevated by DETA/NO treatment. In addition, DETA/NO had no effects on PMN infiltration or LWDR in either animal model nor on the ultrastructure of large airways in rats. This study shows no evidence of pulmonary or hematological toxicity following single or repeated doses of DETA/NO in animals.

Two aerosolized nitric oxide adducts as selective pulmonary vasodilators for acute pulmonary hypertension.

STUDY OBJECTIVES: To determine the selective vasodilatory effects of two inhaled "NONOate" aerosols in a closed chest pig model of acute pulmonary hypertension (APH). METHODS: APH was induced by IV infusion of the prostaglandin H(2)/thromboxane A(2) receptor agonist (U46619). Aerosolized diethylenetriamine nitric oxide (NO) adduct (DETA/NO, n = 4), dipropylenetriamine NO adduct (DPTA/NO, n = 4) [60 micro mol each], or placebo (n = 4) was delivered via the trachea. Hemodynamic parameters and blood samples were measured before and after inhalation therapy. RESULTS: Compared to control animals, pulmonary vascular resistance and pulmonary arterial pressure were significantly reduced from 10 to 105 min after DETA/NO administration and from 10 to 45 min after DPTA/NO aerosol administration (p < 0.05). Both aerosols had no significant effect on systemic vascular resistance or systemic BP. Serum nitrite significantly increased after the inhalation of both NONOates (p < 0.01). There was a tendency for reduced intrapulmonary shunting, particularly after treatment with DETA/NO. CONCLUSION: Both DETA/NO and DPTA/NO administered as aerosols selectively reduced pulmonary hypertension induced by U46619.

The ratio of polymorphonuclear leucocytes (PMN) to non-PMN cells--a novel method of assessing acute lung inflammation.

Polymorphonuclear leucocyte (PMN) numbers are an indicator of the degree of acute lung inflammation. However, there is no standardized system for accurately quantifying their numbers in tissue sections. Also, the effect of lung inflation on the quantification of PMN's is usually overlooked. Lung specimens obtained from clinical biopsies are usually deflated, while inflated lung tissue is commonly used in experimental studies. We report a method, which is independent of the degree of inflation, for measuring the degree of PMN infiltration in the both inflated and non-inflated lungs. Using light microscopy, we counted the numbers of PMN and non-PMN cells in 240 fields from each of five inflated and five non-inflated lung sections and calculated a ratio of PMN: non-PMN cells (the PMN ratio). The effect on accuracy and precision of number of fields counted was investigated by randomly selecting 200, 160, 80 or 40 readings from the original 240 fields. The mean PMN ratio, its 95% confidence interval (CI) and the coefficient of variation (CV) were calculated for each of the four levels of sampling. Both CI and CV increased as the number of readings decreased. Inflated lung tissue had consistently higher values for CV compared to non-inflated lung. In practice, we recommend that for both inflated and non-inflated lungs, 80-160 fields (approximate 0.23-0.45 mm2 of absolute area evaluated) need to be counted to yield a PMN ratio with acceptable accuracy and precision. The PMN ratio provides a simple and objective way of quantifying the degree of acute inflammation in clinical histopathology and experimental toxicology studies involving lungs. It is suitable for use in research of lung inflammation, and as an accessory diagnostic tool and an objective descriptor for clinical histopathology.

Inhaled diazeniumdiolates (NONOates) as selective pulmonary vasodilators.

Selective pulmonary vasodilators cause vasodilatation limited to the pulmonary vasculature, within well-ventilated lung regions. Selective pulmonary vasodilators ideally cause only a minimal effect on the systemic circulation and improve ventilation/perfusion matching. NONOates are a novel group of chemical compounds that spontaneously and continuously release nitric oxide under physiological conditions, over periods of up to 24 h. Inhaled NONOates retain the benefits of gaseous nitric oxide without many of its therapeutic disadvantages. This review focuses on the therapeutic potential of inhaled NONOates in pulmonary hypertension, other lung conditions associated with right ventricular dysfunction and in asthma. The potential toxicity of NONOates is also discussed.