Risk factors and events in the adult intensive care unit associated with pain as self-reported at the end of the intensive care unit stay.

BACKGROUND: The short-term and long-term consequences of the most frequent painful procedures performed in the ICU are unclear. This study aimed to identify the risk factors associated with pain-related discomfort perceived by critically ill patients during the whole ICU stay as self-reported by patients at the end of their ICU stay. METHODS: The study involved 34 ICUs. Adult patients who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Discomforts, including the pain-related discomfort, were assessed using the French 18-item questionnaire on discomfort in ICU patients, the "Inconforts des Patients de REAnimation" (IPREA). Patients scored each item from 0 (minimal discomfort) to 10 (maximal discomfort). Associations between patient characteristics at ICU admission, life support therapies and main potentially painful procedures performed during the ICU stay and pain-related discomfort scores assessed at the end of the ICU stay were analyzed. RESULTS: Patients with complete IPREA questionnaires (n = 2130) were included. The median pain-related discomfort score was 3 (IQR 0-5). From the univariate analysis, pain-related discomfort scores were negatively correlated with age and positively correlated with ICU stay duration; surgical patients reported significant higher pain-related discomfort scores than medical patients; chest drain insertion, chest drain removal, use of bladder catheter, central venous catheter (CVC) insertion, complex dressing change, and intra-hospital transport were associated with pain-related discomfort scores. From the multivariate analyses using generalized estimating equations models, only age, chest drain removal, use of a bladder catheter, CVC insertion, and intra-hospital transport were the main risk factors associated with pain-related discomfort scores. CONCLUSION: Patients who underwent chest drain removal, bladder catheter, CVC insertion, and intra-hospital transport during their ICU stay reported higher pain-related discomfort scores (with respect to the whole ICU stay and assessed at the end of their ICU stay) than patients who did not experience these events. This study may pave the way for further targeted studies aiming at investigating a causal link between these common procedures in the ICU and adult critically ill patients' perceptions of their ICU stay regarding recalled pain. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT02442934, retrospectively registered on May 13, 2015.

Assessment of patients' self-perceived intensive care unit discomforts: Validation of the 18-item version of the IPREA.

BACKGROUND AND AIMS: We reported the validation of the 18-item version of the 'Inconforts des Patients de REAnimation (IPREA)' questionnaire that includes 2 new items exploring feeling depressed and shortness of breath during an intensive care unit (ICU) stay. METHODS: The validation process was integrated in a multicenter, cluster-randomized, controlled, two-parallel group study built to assess the effectiveness of a tailored multicomponent program for reducing self-perceived discomfort in the ICU. All patients aged 18 years or older who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Data collection included demographics (sex, age), type of admission (medical and surgical), health status scores at admission (Knaus score and McCabe index, Simplified Acute Physiology Score (SAPS) II), specific ICU therapeutics such as mechanical ventilation (MV), noninvasive ventilation (NIV), use of vasopressors, or renal replacement therapy (RRT), and ICU stay duration. RESULTS: A total of 994 patients were included. The initial structure of IPREA was confirmed using confirmatory factor analysis showing satisfactory fit (RMSEA at 0.042, CFI at 0.912). No multidimensional structure was identified, allowing the calculation of an overall discomfort score. The three highest discomforts were sleep deprivation, thirst, and perfusion lines and other devices, and the 3 lowest discomforts were limited visiting hours, hunger, and isolation. The overall discomfort score of the 18-item version of IPREA did not differ between men and women. Higher age was significantly correlated with a lower overall discomfort score. While MV was not linked to self-reported discomfort, patients treated by NIV reported higher overall discomfort scores than patients not treated by NIV. CONCLUSION: The 18-item version of IPREA is easy to use and possesses satisfactory psychometric properties. The availability of a reliable and valid French questionnaire asking about patients' self-perceived ICU discomforts enables feedback from the health care team to be incorporated in a continuous quality health care improvement strategy. TRIAL REGISTRATION: clinicaltrial.gov NCT02442934 (registration date: May 18, 2015, retrospectively registered).

Analytical interference during cefepime therapeutic drug monitoring in intensive care patient: About a case report.

ß-lactams therapeutic drug monitoring (TDM) appears as an essential tool to ensure the achievement of pharmacokinetic-pharmacodynamic targets and prevent induced toxicity in intensive care unit patients. Indeed, those patients exhibit important pharmacokinetic variabilities that could lead to unpredictable plasma concentrations, potentially associated with poor clinical outcome, development of antibiotic resistance or increased side effects. Here, we report the case of a 48-year-old-patient admitted to intensive care unit and treated by cefepime using TDM. Due to inconsistency between observed cefepime plasma concentrations and patient clinical examination, investigations were started. After analytical tests, we highlighted an underlying analytical interference that overestimated cefepime plasma concentration with our in-house high performance liquid chromatography with ultraviolet detection (HPLC-UV) method. Only the inadequacy between plasmatic concentration and patient situation alerted pharmacologists and clinicians. As we found no previous case in literature, we believe this report must serve as an example of analytical limits that required pharmacologist awareness and expertise in TDM realization.

Effect of early hyperoxemia on the outcome in servere blunt chest trauma: A propensity score-based analysis of a single-center retrospective cohort.

PURPOSE: Our study aimed to explore the association between early hyperoxemia of the first 24 h on outcomes in patients with severe blunt chest trauma. MATERIALS AND METHODS: In a level I trauma center, we conducted a retrospective study of 426 consecutive patients. Hyperoxemic groups were classified in severe (average PaO2 ≥ 200 mmHg), moderate (≥150 and < 200 mmHg) or mild (≥ 100 and < 200 mmHg) and compared to control group (≥60 and < 100 mmHg) using a propensity score based analysis. The first endpoint was the incidence of a composite outcome including death and hospital-acquired pneumonia occurring from admission to day 28. The secondary endpoints were the incidence of death, the number of hospital-acquired pneumonia, mechanical ventilation-free days and intensive care unit-free day at day 28. RESULTS: The incidence of the composite endpoint was lower in the severe hyperoxemia group(OR, 0.25; 95%CI, 0.09-0.73; P < 0.001) compared with control. The 28-day mortality incidence was lower in severe (OR, 0.23; 95%CI, 0.08-0.68; P < 0.001) hyperoxemia group (OR, 0.41; 95%CI, 0.17-0.97; P = 0.04). Significant association was found between hyperoxemia and secondary outcomes. CONCLUSION: In our cohort early hyperoxemia during the first 24 h of admission after severe blunt chest trauma was not associated with worse outcome.

Circadian disruption of core body temperature in trauma patients: a single-center retrospective observational study.

BACKGROUND: Circadian clock alterations were poorly reported in trauma patients, although they have a critical role in human physiology. Core body temperature is a clinical variable regulated by the circadian clock. Our objective was to identify the circadian temperature disruption in trauma patients and to determine whether these disruptions were associated with the 28-day mortality rate. METHODS: A retrospective and observational single-center cohort study was conducted. All adult severe trauma patients admitted to the intensive care unit of Aix Marseille University, North Hospital, from November 2013 to February 2018, were evaluated. The variations of core body temperature for each patient were analyzed between days 2 and 3 after intensive care unit admission. Core body temperature variations were defined by three parameters: mesor, amplitude, and period. A logistic regression model was used to determine the variables influencing these three parameters. A survival analysis was performed assessing the association between core body temperature rhythm disruption and 28-day mortality rate. A post hoc subgroup analysis focused on the patients with head trauma. RESULTS: Among the 1584 screened patients, 248 were included in this study. The period differed from 24 h in 177 (71%) patients. The mesor value (°C) was associated with body mass index and ketamine use. Amplitude (°C) was associated with ketamine use only. The 28-day mortality rate was 18%. For all trauma patients, age, body mass index, intracranial hypertension, and amplitude were independent risk factors. The patients with a mesor value < 36.9 °C (p < 0.001) and an amplitude > 0.6 °C (p < 0.001) had a higher 28-day mortality rate. Among the patients with head trauma, mesor and amplitude were identified as independent risk factors (HR = 0.40, 95% CI [0.23-0.70], p = 0.001 and HR = 4.73, 95% CI [1.38-16.22], p = 0.01). CONCLUSIONS: Our results highlight an association between core body temperature circadian alteration and 28-day mortality rate. This association was more pronounced in the head trauma patients than in the non-head trauma patients. Further studies are needed to show a causal link and consider possible interventions.

Circadian Rhythm Disruption and Sepsis in Severe Trauma Patients.

BACKGROUND: Circadian rhythms are important regulators of immune functions. Admission to an intensive care unit may impact molecular clock activity and host response. Our objective was to assess and compare the immune circadian rhythms in trauma patients who develop and in those who do not develop sepsis. METHODS: Blood samples were collected from severe trauma patients within 4 days after admission, with collections taking place every 4 h over a 24-h period. Cortisol and cytokines were measured with immunoassays. Whole-blood expression of 3 clock genes (Bmal1, Per2, and Per3) was studied by reverse transcription quantitative polymerase chain reaction. Neutrophils, monocytes, and lymphocytes were analyzed by flow cytometry. Patients with and without sepsis were compared with the cosinor mixed model to estimate mesors, amplitudes, and acrophases. RESULTS: Thirty-eight patients were enrolled in the study, and 13 developed at least 1 septic episode. The septic patients had higher levels of cortisol than the nonseptic patients (mesor at 489 nmol/L vs. 405 nmol/L, P < 0.05) and delayed acrophases (22 h vs. 15 h, P < 0.05). They also had lower lymphocyte counts (mesor at 785 vs. 1,012 cells/µL, P < 0.05), higher neutrophil counts (mesor at 7,648 vs. 7,001 cells/µL, P < 0.05), and monocyte counts (mesor at 579 vs. 473 cells/µL, P < 0.05) than the nonseptic patients. Although no amplitude difference was identified, the acrophases were significantly different between the 2 groups for lymphocytes, interleukin 10 and tumor necrosis factor. CONCLUSION: We demonstrated that all trauma patients had impaired circadian rhythms of cortisol, cytokines, leukocytes, and clock genes. Early circadian disruption was associated with the occurrence of sepsis and might be a marker of sepsis severity.

Tailored multicomponent program for discomfort reduction in critically ill patients may decrease post-traumatic stress disorder in general ICU survivors at 1 year.

PURPOSE: Reducing discomfort in the intensive care unit (ICU) should have a positive effect on long-term outcomes. This study assessed whether a tailored multicomponent program for discomfort reduction was effective in reducing post-traumatic stress disorder (PTSD) symptoms at 1 year in general ICU survivors. METHODS: This study is a prospective observational comparative effectiveness cohort study involving 30 ICUs. It was an extension of the IPREA3 study, a cluster-randomized controlled trial designed to assess the efficacy of a tailored multicomponent program to reduce discomfort in critically ill patients. The program included assessment of ICU-related self-perceived discomforts, immediate and monthly feedback to the healthcare team, and site-specific tailored interventions. The exposure was the implementation of this program. The eligible patients were exposed versus unexposed general adult ICU survivors. The prevalence of substantial PTSD symptoms at 1 year was assessed based on the Impact of Event Scale-Revised (IES-R). RESULTS: Of the 1537 ICU survivors included in the study, 475 unexposed patients and 344 exposed patients had follow-up data at 1 year: 57 (12.0%) and 21 (6.1%) presented with PTSD at 1 year, respectively (p = 0.004). Considering the clustering and after adjusting for age, gender, McCabe classification, and ICU-related self-perceived overall discomfort score, exposed patients were significantly less likely than unexposed patients to have substantial PTSD symptoms at 1 year (p = 0.015). CONCLUSIONS: Implementation of a tailored multicomponent program in the ICU that has proved to be effective for reducing self-perceived discomfort in general adult ICU survivors also reduced the prevalence of substantial PTSD symptoms at 1 year. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02762409.

Implementation of an electronic checklist in the ICU: Association with improved outcomes.

OBJECTIVE: To assess the impact of an electronic checklist during the morning rounds on ventilator-associated pneumonia (VAP) in the intensive care unit (ICU). PATIENTS AND METHODS: We conducted a retrospective, before/after study in a single ICU of a university hospital. A systematic electronic checklist focusing on guidelines adherence was introduced in January 2012. From January 2008 to June 2014, we screened patients with ICU stay durations of at least 48hours. Propensity score-matched analysis with conditional logistic regression was used to compare the rate of VAP and number of days free of invasive devices before and after implementation of the electronic checklist. RESULTS: We analysed 1711 patients (before group, n=761; after group, n=950). The rates of VAP were 21% and 11% in the before and after groups, respectively (p<0.001). In propensity-score matched analysis (n=742 in each group), VAP occurred in 151 patients (21%) during the before period compared with 72 patients (10%) during the after period (odds ratio [OR]=0.38; 95% confidence interval [CI]=0.27-0.53). The after group showed increases in ICU-free days (OR=1.05; 95% CI=1.04-1.07) and mechanical ventilation-free days (OR=1.03; 95% CI=1.01-1.04). CONCLUSION: In this matched before/after study, implementation of an electronic checklist was associated with positive effects on patient outcomes, especially on VAP. Further prospective studies are needed to confirm these observations.

Integrating extended focused assessment with sonography for trauma (eFAST) in the initial assessment of severe trauma: Impact on the management of 756 patients.

BACKGROUND: Before total body computed tomography scan, an initial rapid imaging assessment should be conducted in the trauma bay. It generally includes a chest x-ray, pelvic x-ray, and an extended focused ultrasonography assessment for trauma. This initial imaging assessment has been poorly described since the increase in the use of ultrasound. Therefore, our study aimed to evaluate the diagnostic accuracy and therapeutic impact of this initial imaging work-up in severe trauma patients. A secondary aim was to assess the therapeutic impact of a chest x-ray according to the lung ultrasonography findings. METHODS: Patients with severe trauma who were admitted directly to our level 1 trauma center were consecutively included in this retrospective single center study. The diagnostic accuracy, therapeutic impact, and appropriate decision rate were calculated according to the initial assessment results of the whole body computed tomography scan and surgery reports. RESULTS: Among the 1315 trauma patients admitted, 756 were included in this research. Lung ultrasound showed a higher diagnostic accuracy for haemothorax and pneumothorax cases than the chest x-ray. Sensitivity and specificity of the abdominal ultrasound to detect intraperitoneal effusion were 70% and 96%, respectively. The initial assessment had a therapeutic impact in 76 (10%) of the patients, including 16 (2%) immediate laparotomies and 58 (7%) chest tube insertions. The pelvic x-ray had no therapeutic impact, and when the lung ultrasound was normal, the chest x-ray had a therapeutic impact of only 0.13%. Combining the chest x-ray and lung ultrasound allowed adequate management of all the pneumothorax and haemothorax cases. Only one of the 756 patients had initial management that was judged as inappropriate. This patient had a missed pelvic disjunction with active retroperitoneal bleeding, and underwent an inappropriate immediate laparotomy. CONCLUSIONS: In our cohort, the initial imaging assessment allowed appropriate decisions in 755 of 756 patients, with a global therapeutic impact of 10%. The pelvic x-ray had a minimal therapeutic impact, and in the patients with normal lung ultrasounds, the chest x-ray marginally affected the management of our patients. The potential consequences of abandoning systematic chest and pelvic x-rays should be investigated in future randomized prospective studies.

Risk factors for death in septic shock: A retrospective cohort study comparing trauma and non-trauma patients.

The aim of this study was to compare septic shock directly associated-mortality between severe trauma patients and nontrauma patients to assess the role of comorbidities and age. We conducted a retrospective study in an intensive care unit (ICU) (15 beds) of a university hospital (928 beds). From January 2009 to May 2015, we reviewed 2 anonymized databases including severe trauma patients and nontrauma patients. We selected the patients with a septic shock episode. Among 385 patients (318 nontrauma patients and 67 severe trauma patients), the ICU death rate was 43%. Septic shock was directly responsible for death among 35% of our cohort, representing 123 (39%) nontrauma patients and 10 (15%) trauma patients (P < 0.0). A sequential organ failure assessment score above 12 (odds ratio [OR]: 6.8; 95% confident interval (CI) [1.3-37], P = 0.025) was independently associated with septic shock associated-mortality, whereas severe trauma was a protective factor (OR: 0.26; 95% CI [0.08-0.78], P = 0.01). From these independent risk factors, we determined the probability of septic shock associated-mortality. The receiver-operating characteristics curve has an area under the curve at 0.76 with sensitivity of 55% and specificity of 86%. Trauma appears as a protective factor, whereas the severity of organ failure has a major role in the mortality of septic shock. However, because of the study's design, unmeasured confounding factors should be taken into account in our findings.

A tailored multicomponent program to reduce discomfort in critically ill patients: a cluster-randomized controlled trial.

PURPOSE: Critically ill patients are exposed to stressful conditions and experience several discomforts. The primary objective was to assess whether a tailored multicomponent program is effective for reducing self-perceived discomfort. METHODS: In a cluster-randomized two-arm parallel trial, 34 French adult intensive care units (ICUs) without planned interventions to reduce discomfort were randomized, 17 to the arm including a 6-month period of program implementation followed by a 6-month period without the program (experimental group), and 17 to the arm with an inversed sequence (control group). The tailored multicomponent program consisted of assessment of ICU-related self-perceived discomforts, immediate and monthly feedback to healthcare teams, and site-specific tailored interventions. The primary outcome was the overall discomfort score derived from the 16-item IPREA questionnaire (0, minimal, 100, maximal overall discomfort) and the secondary outcomes were the discomfort scores of each IPREA item. IPREA was administered on the day of ICU discharge with a considered timeframe from the ICU admission until ICU discharge. RESULTS: During a 1-month assessment period, 398 and 360 patients were included in the experimental group and the control group, respectively. The difference (experimental minus control) of the overall discomfort score between groups was - 7.00 (95% CI - 9.89 to - 4.11, p < 0.001). After adjustment (age, gender, ICU duration, mechanical ventilation duration, and type of admission), the program effect was still positive for the overall discomfort score (difference - 6.35, SE 1.23, p < 0.001) and for 12 out of 16 items. CONCLUSIONS: This tailored multicomponent program decreased self-perceived discomfort in adult critically ill patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT02442934.

Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS.

PURPOSE: Prone position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO2/FiO2 ratio <150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS. METHODS: We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed. RESULTS: Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO2 change was found according to oxygenation response or lung morphology. CONCLUSIONS: In ARDS patients with a PaO2/FiO2 ratio ≤150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP.

NOREPINEPHRINE: NOT TOO MUCH, TOO LONG.

The study was designed to assess whether high dosages of norepinephrine are associated with increased death rate and to determine the dosage of norepinephrine associated with an intensive care unit (ICU) death rate greater than 90%. We conducted a retrospective, noninterventional, observational study in a single ICU (15 beds) of an academic hospital. From January 2009 to May 2013, data of all patients with a diagnosis of septic shock were extracted from our database. Data were collected at the time of the admission in ICU, at the onset of septic shock, and when the maximal posology of norepinephrine was reached. Mortality was assessed in ICU, in hospital, and at day 90. Among the 324 patients with septic shock, the death rate was 48%. The death rate reached 90% for the quantile of patients receiving more than 1 µg/kg per minute of norepinephrine. In our cohort, four independent factors associated with mortality were identified: age (odds ratio, 1.02 [95% confidence interval, 1.00-1.04]; P = 0.02), thrombocytopenia (odds ratio, 3.8 [95% confidence interval, 1.8-8.5]; P < 0.001), urine output less than 500 mL (odds ratio, 8.7 [95% confidence interval, 3.6-25]; P < 0.001), and dosage of norepinephrine greater than 1 µg/kg per minute (odds ratio, 9.7 [95% confidence interval, 4.5-23]; P < 0.001). However, because of the study's design, unmeasured confounding factors should be taken into account in our findings.

Point-of-care ultrasound in intensive care units: assessment of 1073 procedures in a multicentric, prospective, observational study.

OBJECTIVE: To describe current use and diagnostic and therapeutic impacts of point-of-care ultrasound (POCUS) in the intensive care unit (ICU). BACKGROUND: POCUS is of growing importance in the ICU. Several guidelines recommend its use for procedural guidance and diagnostic assessment. Nevertheless, its current use and clinical impact remain unknown. METHODS: Prospective multicentric study in 142 ICUs in France, Belgium, and Switzerland. All the POCUS procedures performed during a 24-h period were prospectively analyzed. Data regarding patient condition and the POCUS procedures were collected. Factors associated with diagnostic and therapeutic impacts were identified. RESULTS: Among 1954 patients hospitalized during the study period, 1073 (55%) POCUS/day were performed in 709 (36%) patients. POCUS served for diagnostic assessment in 932 (87%) cases and procedural guidance in 141 (13%) cases. Transthoracic echocardiography, lung ultrasound, and transcranial Doppler accounted for 51, 17, and 16% of procedures, respectively. Diagnostic and therapeutic impacts of diagnostic POCUS examinations were 84 and 69%, respectively. Ultrasound guidance was used in 54 and 15% of cases for central venous line and arterial catheter placement, respectively. Hemodynamic instability, emergency conditions, transthoracic echocardiography, and ultrasounds performed by certified intensivists themselves were independent factors affecting diagnostic or therapeutic impacts. CONCLUSIONS: With regard to guidelines, POCUS utilization for procedural guidance remains insufficient. In contrast, POCUS for diagnostic assessment is of extensive use. Its impact on both diagnosis and treatment of ICU patients seems critical. This study identified factors associated with an improved clinical value of POCUS.