Multicenter International Cohort Validation of a Modified Sequential Organ Failure Assessment Score Using the Richmond Agitation-sedation Scale.

OBJECTIVE: In a multicenter, international cohort, we aimed to validate a modified Sequential Organ Failure Assessment (mSOFA) using the Richmond Agitation-Sedation Scale, hypothesized as comparable to the Glasgow Coma Scale (GCS)-based Sequential Organ Failure Assessment (SOFA). SUMMARY BACKGROUND DATA: The SOFA score, whose neurologic component is based on the GCS, can predict intensive care unit (ICU) mortality. But, GCS is often missing in lieu of other assessments, such as the also reliable and validated Richmond Agitation Sedation Scale (RASS). Single-center data suggested an RASS-based SOFA (mSOFA) predicted ICU mortality. METHODS: Our nested cohort within the prospective 2016 Fourth International Study of Mechanical Ventilation contains 4120 ventilated patients with daily RASS and GCS assessments (20,023 patient-days, 32 countries). We estimated GCS from RASS via a proportional odds model without adjustment. ICU mortality logistic regression models and c-statistics were constructed using SOFA (measured GCS) and mSOFA (measured RASS-estimated GCS), adjusted for age, sex, body-mass index, region (Europe, USA-Canada, Latin America, Africa, Asia, Australia-New Zealand), and postoperative status (medical/surgical). RESULTS: Cohort-wide, the mean SOFA=9.4+/-2.8 and mean mSOFA = 10.0+/-2.3, with ICU mortality = 31%. Mean SOFA and mSOFA similarly predicted ICU mortality (SOFA: AUC = 0.784, 95% CI = 0.769-0.799; mSOFA: AUC = 0.778, 95% CI = 0.763-0.793, P = 0.139). Across models, other predictors of mortality included higher age, female sex, medical patient, and African region (all P < 0.001). CONCLUSIONS: We present the first SOFA modification with RASS in a "real-world" international cohort. Estimating GCS from RASS preserves predictive validity of SOFA to predict ICU mortality. Alternative neurologic measurements like RASS can be viably integrated into severity of illness scoring systems like SOFA.

Relationships Between Resting Energy Expenditure and Transcranial Doppler Measurements in Patients With and Without Brain Death.

Introduction Brain metabolism deteriorates during brain death, suggesting that cerebral metabolic measurements could serve as a prognostic factor. The application of transcranial Doppler can be useful in evaluating patients evolving to brain death. Resting energy expenditure is lower than expected in patients with brain death, and this is caused by the decrease in cerebral blood flow and consequently lower oxygen supply. The primary aim of this retrospective study is to investigate the early metabolic changes in patients with clinical criteria of brain death and examine if these changes are related to a gradual decrease in blood flow velocities in the middle cerebral artery. Methods All consecutive patients from 1st June 2018 to 30th April 2022, admitted to the ICU with brain injury and a GCS ≤ 8, were included retrospectively in the study. Patients were allocated into two groups: Group A, patients without clinical signs of brain death (n = 32), and Group B, patients with brain death (n = 34). In each group, three sets of metabolic measurements were performed concomitantly with cerebral blood flow velocities using transcranial Doppler (a) upon admission to the ICU, (b) once hemodynamic stabilization was obtained, and (c) 48 hours after their hemodynamic stabilization or when brain death was confirmed by clinical criteria. Resting energy expenditure (REE) measurements were performed using a metabolic computer. Cerebral blood flow velocities were measured after a period of 30 min using a 2-MHZ 2D ultrasound probe. Results Brain-dead patients had a significant decrease in their metabolic parameters as the cerebral blood flow velocities recorded with the transcranial Doppler deteriorated, (REE Group A = 1667.65 ± 597 vs Group B = 1376.12 ± 615, p = 0.05 and REE predicted Group A = 113.19 ± 44.9 vs Group B = 93.29 ± 41.5, p = 0.066 for measurement 1; REE Group A = 1844 ± 530.9 vs Group B = 1219.97 ± 489, p < 0.001 and REE predicted Group A = 124.38 ± 39 vs Group B = 81.35 ± 30.4, p < 0.001 for measurement 2; REE Group A = 1750.97 ± 414, p < 0.001 and REE predicted Group A = 116.38 ± 19.2 vs Group B = 56.09 ± 19.6, p < 0.001 for measurement 3). Multiple stepwise regression analysis revealed a strong relationship between age, the worsening of the blood flow velocities pattern, and the decrease in REE (multiple R = 0.264, F = 5.55, p = 0.009). Furthermore, a statistically significant correlation was found between temperature and REE (correlation coefficient = 0.500, 0.674, 0.784 for measurements 1, 2, and 3, respectively, and p < 0.001 for all measures). Conclusions In brain-dead patients, the gradual decrease in cerebral blood flow leads to a decrease in REE as well as thermogenetic control. These changes can be detected early after the patient's admission to the ICU.

Ultrasonographic assessment of diaphragmatic contraction and relaxation properties: correlations of diaphragmatic displacement with oesophageal and transdiaphragmatic pressure.

Transdiaphragmatic (Pdi) and oesophageal pressures (Pes) are useful in understanding the pathophysiology of the respiratory system. They provide insight into respiratory drive, intrinsic positive end-expiratory pressure, diaphragmatic fatigue and weaning failure. BACKGROUND: The use of Pdi and Pes in clinical practice is restricted due to the invasiveness of the technique and the cumbersome equipment needed. On the other hand, diaphragmatic displacement is non-invasively and easily assessed with M-mode ultrasound. PURPOSE: We observed striking similarities in shape and magnitude between M-mode diaphragmatic displacement, Pes and Pdi pressures. The study aimed to evaluate if the information provided by these two pressures could be obtained non-invasively from the diaphragmatic displacement curve. MATERIAL AND METHODS: In 14 consecutive intubated patients undergoing a weaning trial, simultaneous recordings of Pes and Pdi pressures and the diaphragmatic displacement were assessed while breathing spontaneously and during a sniff-like manoeuvre. Moreover, the slope of the diaphragmatic displacement curve during relaxation was compared with the maximal relaxation rate (MRR) obtained from the Pdi curve. RESULTS: More than 200 breaths were analysed in pairs. Diaphragmatic displacement significantly correlated with Pdi (R2=0.33, p<0.001) and Pes (R2=0.44, p<0.001), and this correlation further improved during sniff (R2=0.47, p<0.001) and (R2=0.64, p<0.001), respectively. Additionally, a significant correlation was found between the relaxation slope derived from the diaphragmatic displacement curve and the MRR derived from the Pdi curve, both in normal breathing (R2=0.379, p<0.001) and during the sniff manoeuvre (R2=0.71, p<0.001). CONCLUSIONS: M-mode diaphragmatic displacement parameters correlate well with the ones obtained from oesophageal pressure and Pdi, particularly during sniffing. Diaphragmatic displacement assessment possibly offers an alternative non-invasive solution for understanding and clinically monitoring the diaphragmatic contractile properties and weaning failure due to diaphragmatic fatigue.

Tissue Doppler Imaging of the Diaphragm in Healthy Subjects and Critically Ill Patients.

Rationale: Tissue Doppler imaging (TDI) is an echocardiographic method that measures the velocity of moving tissue.Objectives: We applied this technique to the diaphragm to assess the velocity of diaphragmatic muscle motion during contraction and relaxation.Methods: In 20 healthy volunteers, diaphragmatic TDI was performed to assess the pattern of diaphragmatic motion velocity, measure its normal values, and determine the intra- and interobserver variability of measurements. In 116 consecutive ICU patients, diaphragmatic excursion, thickening, and TDI parameters of peak contraction velocity, peak relaxation velocity, velocity-time integral, and TDI-derived maximal relaxation rate were assessed during weaning. In a subgroup of 18 patients, transdiaphragmatic pressure (Pdi)-derived parameters (peak Pdi, pressure-time product, and diaphragmatic maximal relaxation rate) were recorded simultaneously with TDI.Measurements and Main Results: In terms of reproducibility, the intercorrelation coefficients were >0.89 for all TDI parameters (P < 0.001). Healthy volunteers and weaning success patients exhibited lower values for all TDI parameters compared with weaning failure patients, except for velocity-time integral, as follows: peak contraction velocity, 1.35 ± 0.34 versus 1.50 ± 0.59 versus 2.66 ± 2.14 cm/s (P < 0.001); peak relaxation velocity, 1.19 ± 0.39 versus 1.53 ± 0.73 versus 3.36 ± 2.40 cm/s (P < 0.001); and TDI-maximal relaxation rate, 3.64 ± 2.02 versus 10.25 ± 5.88 versus 29.47 ± 23.95 cm/s2 (P < 0.001), respectively. Peak contraction velocity was strongly correlated with peak transdiaphragmatic pressure and pressure-time product, whereas Pdi-maximal relaxation rate was significantly correlated with TDI-maximal relaxation rate.Conclusions: Diaphragmatic tissue Doppler allows real-time assessment of the diaphragmatic tissue motion velocity. Diaphragmatic TDI-derived parameters differentiate patients who fail a weaning trial from those who succeed and correlate well with Pdi-derived parameters.

International Analgesia, Sedation, and Delirium Practices: a prospective cohort study.

BACKGROUND: While understanding of critical illness and delirium continue to evolve, the impact on clinical practice is often unknown and delayed. Our purpose was to provide insight into practice changes by characterizing analgesia and sedation usage and occurrence of delirium in different years and international regions. METHODS: We performed a retrospective analysis of two multicenter, international, prospective cohort studies. Mechanically ventilated adults were followed for up to 28 days in 2010 and 2016. Proportion of days utilizing sedation, analgesia, and performance of a spontaneous awakening trial (SAT), and occurrence of delirium were described for each year and region and compared between years. RESULTS: A total of 14,281 patients from 6 international regions were analyzed. Proportion of days utilizing analgesia and sedation increased from 2010 to 2016 (p < 0.001 for each). Benzodiazepine use decreased in every region but remained the most common sedative in Africa, Asia, and Latin America. Performance of SATs increased overall, driven mostly by the US/Canada region (24 to 35% of days with sedation, p < 0.001). Any delirium during admission increased from 7 to 8% of patients overall and doubled in the US/Canada region (17 to 36%, p < 0.001). CONCLUSIONS: Analgesia and sedation practices varied widely across international regions and significantly changed over time. Opportunities for improvement in care include increasing delirium monitoring, performing SATs, and decreasing use of sedation, particularly benzodiazepines.

A New Method for Diaphragmatic Maximum Relaxation Rate Ultrasonographic Measurement in the Assessment of Patients With Diaphragmatic Dysfunction.

Measurements of ultrasound diaphragmatic motion, amplitude, force, and velocity of contraction may provide important and essential information about diaphragmatic fatigue, weakness, or paralysis. In this paper, we propose and evaluate a semi-automated analysis system for measuring the diaphragmatic motion and estimating the maximum relaxation rate (MRR_SAUS) from ultrasound M-mode images of the diaphragmatic muscle. The system was evaluated on 27 M-mode ultrasound images of the diaphragmatic muscle [20 with no resistance (NRES) and 7 with resistance (RES)]. We computed semi-automated ultrasound MRR measurements on all NRES/RES images, using the proposed system (MRR_SAUS = 3.94 ± 0.91/4.98 ± 1.98 [1/s]), and compared them with the manual measurements made by a clinical expert (MRR_MUS = 2.36 ± 1.19/5.8 ± 2.1 [1/s],) and those made by a reference manual method (MRR_MB = 3.93 ± 0.89/3.73 ± 0.52 [1/sec], performed manually with the Biopac system. MRR_SAUS and MRR_MB measurements were not statistically significantly different for NRES and RES subjects but were significantly different with the MRR-MUS measurements made by the clinical expert. It is anticipated that the proposed system might be used in the future in the clinical practice in the assessment and follow up of patients with diaphragmatic weakness or paralysis. It may thus potentially help to understand post-operative pulmonary dysfunction or weaning failure from mechanical ventilation. Further validation and additional experimentation in a larger sample of images and different patient groups is required for further validating the proposed system.

Prediction and Outcome of Intensive Care Unit-Acquired Paresis.

BACKGROUND: Intensive care unit-acquired paresis (ICUAP) is associated with poor outcomes. Our objective was to evaluate predictors for ICUAP and the short-term outcomes associated with this condition. METHODS: A secondary analysis of a prospective study including 4157 mechanically ventilated adults in 494 intensive care units from 39 countries. After sedative interruption, patients were screened for ICUAP daily, which was defined as the presence of symmetric and flaccid quadriparesis associated with decreased or absent deep tendon reflexes. A multinomial logistic regression was used to create a predictive model for ICUAP. Propensity score matching was used to estimate the relationship between ICUAP and short-term outcomes (ie, weaning failure and intensive care unit [ICU] mortality). RESULTS: Overall, 114 (3%) patients had ICUAP. Variables associated with ICUAP were duration of mechanical ventilation (relative risk ratio [RRR] per day, 1.10; 95% confidence interval [CI] 1.08-1.12), steroid therapy (RRR 1.8; 95% CI, 1.2-2.8), insulin therapy (RRR 1.8; 95% CI 1.2-2.7), sepsis (RRR 1.9; 95% CI: 1.2 to 2.9), acute renal failure (RRR 2.2; 95% CI 1.5-3.3), and hematological failure (RRR 1.9; 95% CI: 1.2-2.9). Coefficients were used to generate a weighted scoring system to predict ICUAP. ICUAP was significantly associated with both weaning failure (paired rate difference of 22.1%; 95% CI 9.8-31.6%) and ICU mortality (paired rate difference 10.5%; 95% CI 0.1-24.0%). CONCLUSIONS: Intensive care unit-acquired paresis is relatively uncommon but is significantly associated with weaning failure and ICU mortality. We constructed a weighted scoring system, with good discrimination, to predict ICUAP in mechanically ventilated patients at the time of awakening.

The impact of healthcare professionals' personality and religious beliefs on the decisions to forego life sustaining treatments: an observational, multicentre, cross-sectional study in Greek intensive care units.

OBJECTIVES: To assess the opinion of intensive care unit (ICU) personnel and the impact of their personality and religious beliefs on decisions to forego life-sustaining treatments (DFLSTs). SETTING: Cross-sectional, observational, national study in 18 multidisciplinary Greek ICUs, with >6 beds, between June and December 2015. PARTICIPANTS: 149 doctors and 320 nurses who voluntarily and anonymously answered the End-of-Life (EoL) attitudes, Personality (EPQ) and Religion (SpREUK) questionnaires. Multivariate analysis was used to detect the impact of personality and religious beliefs on the DFLSTs. RESULTS: The participation rate was 65.7%. Significant differences in DFLSTs between doctors and nurses were identified. 71.4% of doctors and 59.8% of nurses stated that the family was not properly informed about DFLST and the main reason was the family's inability to understand medical details. 51% of doctors expressed fear of litigation and 47% of them declared that this concern influenced the information given to family and nursing staff. 7.5% of the nurses considered DFLSTs dangerous, criminal or illegal. Multivariate logistic regression identified that to be a nurse and to have a high neuroticism score were independent predictors for preferring the term 'passive euthanasia' over 'futile care' (OR 4.41, 95% CI 2.21 to 8.82, p<0.001, and OR 1.59, 95% CI 1.03 to 2.72, p<0.05, respectively). Furthermore, to be a nurse and to have a high-trust religious profile were related to unwillingness to withdraw mechanical ventilation. Fear of litigation and non-disclosure of the information to the family in case of DFLST were associated with a psychoticism personality trait (OR 2.45, 95% CI 1.25 to 4.80, p<0.05). CONCLUSION: We demonstrate that fear of litigation is a major barrier to properly informing a patient's relatives and nursing staff. Furthermore, aspects of personality and religious beliefs influence the attitudes of ICU personnel when making decisions to forego life-sustaining treatments.

Burnout and job satisfaction of intensive care personnel and the relationship with personality and religious traits: An observational, multicenter, cross-sectional study.

OBJECTIVES: To investigate if burnout in the Intensive Care Unit (ICU) is influenced by aspects of personality, religiosity and job satisfaction. RESEARCH METHODOLOGY: Cross-sectional study, designed to assess burnout in the ICU and to investigate possible determinants. Three different questionnaires were used: the Malach Burnout Inventory, the Eysenck Personality Questionnaire and the Spiritual/Religious Attitudes Questionnaire. Predicting factors for high burnout were identified by multivariate logistic regression analysis. SETTING/PARTICIPANTS: This national study was addressed to physicians and nurses working full-time in 18 Greek ICU departments from June to December 2015. RESULTS: The participation rate was 67.9% (n=149) and 65% (n=320) for ICU physicians and nurses, respectively). High job satisfaction was recorded in both doctors (80.8%) and nurses (63.4%). Burnout was observed in 32.8% of the study participants, higher in nurses compared to doctors (p<0.001). Multivariate analysis revealed that neuroticism was a positive and extraversion a negative predictor of exhaustion (OR 5.1, 95%CI 2.7-9.7, p<0.001 and OR 0.49, 95%CI 0.28-0.87, p=0.014, respectively). Moreover, three other factors were identified: Job satisfaction (OR 0.26, 95%CI 0.14-0.48, p<0.001), satisfaction with current End-of-Life care (OR 0.41, 95%CI 0.23-0.76, p=0.005) and isolation feelings after decisions to forego life sustaining treatments (OR 3.48, 95%CI 1.25-9.65, p=0.017). CONCLUSIONS: Personality traits, job satisfaction and the way End-of-Life care is practiced influence burnout in the ICU.

Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome.

PURPOSE: To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS). PATIENTS AND METHODS: We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality. MAIN OUTCOMES: We included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48 h and mortality suggests higher mortality at or above PaCO2 of ≥50 mmHg. Patients with severe hypercapnia (PaCO2 ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04-2.41; p = 0.032). CONCLUSIONS: Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01093482.

Association between ventilatory settings and development of acute respiratory distress syndrome in mechanically ventilated patients due to brain injury.

PURPOSE: In neurologically critically ill patients with mechanical ventilation (MV), the development of acute respiratory distress syndrome (ARDS) is a major contributor to morbidity and mortality, but the role of ventilatory management has been scarcely evaluated. We evaluate the association of tidal volume, level of PEEP and driving pressure with the development of ARDS in a population of patients with brain injury. MATERIALS AND METHODS: We performed a secondary analysis of a prospective, observational study on mechanical ventilation. RESULTS: We included 986 patients mechanically ventilated due to an acute brain injury (hemorrhagic stroke, ischemic stroke or brain trauma). Incidence of ARDS in this cohort was 3%. Multivariate analysis suggested that driving pressure could be associated with the development of ARDS (odds ratio for unit increment of driving pressure 1.12; confidence interval for 95%: 1.01 to 1.23) whereas we did not observe association for tidal volume (in ml per kg of predicted body weight) or level of PEEP. ARDS was associated with an increase in mortality, longer duration of mechanical ventilation, and longer ICU length of stay. CONCLUSIONS: In a cohort of brain-injured patients the development of ARDS was not common. Driving pressure was associated with the development of this disease.

Impact of sedation and analgesia during noninvasive positive pressure ventilation on outcome: a marginal structural model causal analysis.

PURPOSE: There are limited data available about the role of sedation and analgesia during noninvasive positive pressure ventilation (NPPV). The objective of study was to estimate the effect of analgesic or sedative drugs on the failure of NPPV. METHODS: We studied patients who received at least 2 h of NPPV as first-line therapy in a prospective observational study carried out in 322 intensive care units from 30 countries. A marginal structural model (MSM) was used to analyze the association between the use of analgesic or sedative drugs and NPPV failure (defined as need for invasive mechanical ventilation). RESULTS: 842 patients were included in the analysis. Of these, 165 patients (19.6%) received analgesic or sedative drugs at some time during NPPV; 33 of them received both. In the adjusted analysis, the use of analgesics (odds ratio 1.8, 95% confidence interval 0.6-5.4) or sedatives (odds ratio 2.8, 95% CI 0.85-9.4) alone was not associated with NPPV failure, but their combined use was associated with failure (odds ratio 5.7, 95% CI 1.8-18.4). CONCLUSIONS: Slightly less than 20% of patients received analgesic or sedative drugs during NPPV, with no apparent effect on outcome when used alone. However, the simultaneous use of analgesics and sedatives may be associated with failure of NPPV.

Targeting occult heart failure in intensive care unit patients with acute chronic obstructive pulmonary disease exacerbation: effect on outcome and quality of life.

PURPOSE: To estimate the prevalence of previously undiagnosed heart failure in mechanically ventilated patients with severe exacerbation of chronic obstructive pulmonary disease (COPD) and to evaluate the impact of specific heart failure treatment on patients' outcome. MATERIALS AND METHODS: In this prospective study, we included 107 consecutive patients with COPD without known history of cardiac disease who were admitted to the intensive care unit (ICU) because of hypercapnic respiratory failure leading to mechanical ventilation. RESULTS: Patients were divided into 4 groups according to the echocardiographic findings: patients with isolated right or left ventricular failure, biventricular failure, and normal heart function. Three of 4 patients demonstrated findings of heart failure. In 41%, the presence of previously unrecognized left ventricular dysfunction was revealed. Patients with isolated left ventricular dysfunction experienced less days on mechanical ventilation, less intensive care unit days, improved quality of life, and decreased in-hospital and 6-month mortality compared with patients with normal heart. CONCLUSIONS: In mechanically ventilated patients with severe exacerbation of COPD, unrecognized left or right ventricular failure is common. Among patients with isolated left ventricular failure, the early detection and appropriate treatment improves long-term quality of life and may decrease the short- and 6-month morbidity and mortality.

Evolution of mortality over time in patients receiving mechanical ventilation.

RATIONALE: Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES: To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS: Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS: We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS: Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).