Monitoring delirium in the intensive care unit: Diagnostic accuracy of the CAM-ICU tool when performed by certified nursing assistants - A prospective multicenter study.

BACKGROUND: Monitoring delirium in critically ill patients is recognized as a major challenge. Although involving certified nursing assistants could be a valuable help in this field, such strategy has never been formally investigated. OBJECTIVES: Following theoretical training, we conducted a prospective multicenter study assessing the diagnostic accuracy of a CAM-ICU delirium screening strategy performed by CNAs in clinical settings, compared to parallel blinded evaluations conducted by nurses and physicians. METHODS: From October 2020 to June 2022, adult intensive care patients admitted in three French University teaching hospitals with Richmond Agitation Sedation Scale ≥-2 were independently assessed for delirium by the three members of the care team (clinical nursing assistant, nurse and physician) using CAM-ICU in a random order. Physician's assessment served as the reference standard for comparisons. RESULTS: We analyzed results from 268 triplets of CAM-ICU assessments performed sequentially on 203 patients. Prevalence of delirium was 22%. Compared to physician's assessments, clinical nursing assistants demonstrated a sensitivity (Se) of 88% CI95% [80-96] and a specificity (Sp) of 95% [92-98] in detecting delirium. There was no significant difference in the performance of clinical nursing assistants and nurses (Se = 90 % [82-97] p = 0.77, Sp = 98 % [95-100] p = 0.19). We observed high agreement between results obtained by physicians and clinical nursing assistants (ĸ = 0.82) and clinical nursing assistants performance remained consistent in the subgroups at higher risk of delirium. CONCLUSION: Evaluation of the CAM-ICU by clinical nursing assistants is feasible and should be seen as an opportunity to increase routine monitoring of delirium in intensive care patients. IMPLICATION FOR CLINICAL PRACTICE: Delirium is a severe and underestimated complication of intensive care unit stay. This study results demonstrate the great performance of trained clinical nursing assistants in detecting delirium using the CAM-ICU. Further research is needed to define the most effective role for clinical nursing assistants in the routine management of delirium in intensive care patients.

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation.

BACKGROUND: The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation. METHODS: This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37). RESULTS: The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0-51] and 0 [0-43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups. CONCLUSIONS: In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.

Acyclovir for Mechanically Ventilated Patients With Herpes Simplex Virus Oropharyngeal Reactivation: A Randomized Clinical Trial.

Importance: The role of herpes simplex virus (HSV) reactivation on morbidity and mortality in patients in the intensive care unit requiring mechanical ventilation remains unknown. Objective: To determine whether preemptive treatment with intravenous acyclovir reduces the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation. Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted in 16 intensive care units in France. Participants included 239 adults (age, >18 years) who received mechanical ventilation for at least 96 hours and continued to receive mechanical ventilation for 48 hours or more, with HSV oropharyngeal reactivation. Patients were enrolled between February 2, 2014, and February 22, 2018. Interventions: Participants were randomized to receive intravenous acyclovir, 5 mg/kg, 3 times daily for 14 days or a matching placebo. Main Outcomes and Measures: The primary end point was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included mortality at 60 days. Main analyses were conducted on an intention-to-treat basis. Results: Of 239 patients enrolled and randomized, 1 patient withdrew consent, leaving 238 patients, with 119 patients in both the acyclovir and placebo (control) groups (median [IQR] age, 61 [50-70] years; 76 [32%] women) available for primary outcome measurement. On day 60, the median (IQR) numbers of ventilator-free days were 35 (0-53) for acyclovir recipients and 36 (0-50]) for controls (P = .17 for between-group comparison). Among secondary outcomes, 26 patients (22%) and 39 patients (33%) had died at day 60 (risk difference, 0.11, 95% CI, -0.004 to 0.22, P = .06). The adverse event frequency was similar for both groups (28% in the acyclovir group and 23% in the placebo group, P = .40), particularly acute renal failure post randomization affecting 3 acyclovir recipients (3%) and 2 controls (2%). Four patients (3%) in the acyclovir group vs none in the placebo group stopped the study drug for treatment-related adverse events. Conclusions and Relevance: In patients receiving mechanical ventilation for 96 hours or more with HSV reactivation in the throat, use of acyclovir, 5 mg/kg, 3 times daily for 14 days, did not increase the number of ventilator-free days at day 60, compared with placebo. These findings do not appear to support routine preemptive use of acyclovir in this setting. Trial Registration: ClinicalTrials.gov identifier: NCT02152358.

Soluble form of the receptor for advanced glycation end products is a marker of acute lung injury but not of severe sepsis in critically ill patients.

OBJECTIVES: Levels of the soluble form of the receptor for advanced glycation end products (sRAGE) are elevated during acute lung injury. However, it is not known whether this increase is linked to its involvement in alveolar epithelium injury or in systemic inflammation. Whether sRAGE is a marker of acute lung injury and acute respiratory distress syndrome, regardless of associated severe sepsis or septic shock, remains unknown in the intensive care unit setting. DESIGN: Prospective, observational, clinical study. SETTING: Intensive care unit of an academic medical center. PATIENTS: A total of 64 consecutive subjects, divided into four groups: acute lung injury/acute respiratory distress syndrome (n=15); acute lung injury/acute respiratory distress syndrome plus severe sepsis/septic shock (n=18); severe sepsis/septic shock (n=16); and mechanically ventilated controls (n=15). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma sRAGE levels were measured at baseline and on days 3, 6, and 28 (or at intensive care unit discharge, whichever occurred first). Baseline plasma levels of sRAGE were significantly higher in patients with acute lung injury/acute respiratory distress syndrome, with (median, 2951 pg/mL) or without (median, 3761 pg/mL) severe sepsis, than in patients with severe sepsis (median, 488 pg/mL) only and in mechanically ventilated controls (median, 525 pg/mL). Levels of sRAGE were correlated with acute lung injury/acute respiratory distress syndrome severity and decreased over time but were not associated with outcome. Lower baseline plasma sRAGE was associated with focal loss of aeration based on computed tomography lung morphology. CONCLUSIONS: sRAGE levels were elevated during acute lung injury/acute respiratory distress syndrome, regardless of the presence or absence of severe sepsis. The plasma level of sRAGE was correlated with clinical and radiographic severity in acute respiratory distress syndrome patients and decreased over time, suggesting resolution of the injury to the alveolar epithelium. Further study is warranted to test the clinical utility of this biomarker in managing such patients and to better understand its relationship with lung morphology during acute lung injury/acute respiratory distress syndrome.

A recruitment maneuver increases oxygenation after intubation of hypoxemic intensive care unit patients: a randomized controlled study.

INTRODUCTION: Tracheal intubation and anaesthesia promotes lung collapse and hypoxemia. In acute lung injury patients, recruitment maneuvers (RMs) increase lung volume and oxygenation, and decrease atelectasis. The aim of this study was to evaluate the efficacy and safety of RMs performed immediately after intubation. METHODS: This randomized controlled study was conducted in two 16-bed medical-surgical intensive care units within the same university hospital. Consecutive patients requiring intubation for acute hypoxemic respiratory failure were included. Patients were randomized to undergo a RM immediately (within 2 minutes) after intubation, consisting of a continuous positive airway pressure (CPAP) of 40 cmH2O over 30 seconds (RM group), or not (control group). Blood gases were sampled and blood samples taken for culture before, within 2 minutes, 5 minutes, and 30 minutes after intubation. Haemodynamic and respiratory parameters were continuously recorded throughout the study. Positive end expiratory pressure (PEEP) was set at 5 cmH2O throughout. RESULTS: The control (n = 20) and RM (n = 20) groups were similar in terms of age, disease severity, diagnosis at time of admission, and PaO2 obtained under 10-15 L/min oxygen flow immediately before (81 +/- 15 vs 83 +/- 35 mmHg, P = 0.9), and within 2 minutes after, intubation under 100% FiO2 (81 +/- 15 vs 83 +/- 35 mmHg, P = 0.9). Five minutes after intubation, PaO2 obtained under 100% FiO2 was significantly higher in the RM group compared with the control group (93 +/- 36 vs 236 +/- 117 mmHg, P = 0.008). The difference remained significant at 30 minutes with 110 +/- 39 and 180 +/- 79 mmHg, respectively, for the control and RM groups. No significant difference in haemodynamic conditions was observed between groups at any time. Following tracheal intubation, 15 patients had positive blood cultures, showing microorganisms shared with tracheal aspirates, with no significant difference in the incidence of culture positivity between groups. CONCLUSIONS: Recruitment maneuver following intubation in hypoxemic patients improved short-term oxygenation, and was not associated with increased adverse effects. TRIAL REGISTRATION: NCT01014299.

Respiratory effects of different recruitment maneuvers in acute respiratory distress syndrome.

INTRODUCTION: Alveolar derecruitment may occur during low tidal volume ventilation and may be prevented by recruitment maneuvers (RMs). The aim of this study was to compare two RMs in acute respiratory distress syndrome (ARDS) patients. METHODS: Nineteen patients with ARDS and protective ventilation were included in a randomized crossover study. Both RMs were applied in each patient, beginning with either continuous positive airway pressure (CPAP) with 40 cm H2O for 40 seconds or extended sigh (eSigh) consisting of a positive end-expiratory pressure maintained at 10 cm H2O above the lower inflection point of the pressure-volume curve for 15 minutes. Recruited volume, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2), and hemodynamic parameters were recorded before (baseline) and 5 and 60 minutes after RM. All patients had a lung computed tomography (CT) scan before study inclusion. RESULTS: Before RM, PaO2/FiO2 was 151 +/- 61 mm Hg. Both RMs increased oxygenation, but the increase in PaO2/FiO2 was significantly higher with eSigh than CPAP at 5 minutes (73% +/- 25% versus 44% +/- 28%; P < 0.001) and 60 minutes (68% +/- 23% versus 35% +/- 22%; P < 0.001). Only eSigh significantly increased recruited volume at 5 and 60 minutes (21% +/- 22% and 21% +/- 25%; P = 0.0003 and P = 0.001, respectively). The only difference between responders and non-responders was CT lung morphology. Eleven patients were considered as recruiters with eSigh (10 with diffuse loss of aeration) and 6 with CPAP (5 with diffuse loss of aeration). During CPAP, 2 patients needed interruption of RM due to a drop in systolic arterial pressure. CONCLUSION: Both RMs effectively increase oxygenation, but CPAP failed to increase recruited volume. When the lung is recruited with an eSigh adapted for each patient, alveolar recruitment and oxygenation are superior to those observed with CPAP.

Response to recruitment maneuver influences net alveolar fluid clearance in acute respiratory distress syndrome.

BACKGROUND: Alveolar fluid clearance is impaired in the majority of patients with acute respiratory distress syndrome (ARDS). Experimental studies have shown that a reduction of tidal volume increases alveolar fluid clearance. This study was aimed at assessing the impact of the response to a recruitment maneuver (RM) on net alveolar fluid clearance. METHODS: In 15 patients with ARDS, pulmonary edema fluid and plasma protein concentrations were measured before and after an RM, consisting of a positive end-expiratory pressure maintained 10 cm H2O above the lower inflection point of the pressure-volume curve during 15 min. Cardiorespiratory parameters were measured at baseline (before RM) and 1 and 4 h later. RM-induced lung recruitment was measured using the pressure-volume curve method. Net alveolar fluid clearance was measured by measuring changes in bronchoalveolar protein concentrations before and after RM. RESULTS: In responders, defined as patients showing an RM-induced increase in arterial oxygen tension of 20% of baseline value or greater, net alveolar fluid clearance (19 +/- 13%/h) and significant alveolar recruitment (113 +/- 101 ml) were observed. In nonresponders, neither net alveolar fluid clearance (-24 +/- 11%/h) nor alveolar recruitment was measured. Responders and nonresponders differed only in terms of lung morphology: Responders had a diffuse loss of aeration, whereas nonresponders had a focal loss of aeration, predominating in the lower lobes. CONCLUSION: In the absence of alveolar recruitment and improvement in arterial oxygenation, RM decreases the rate of alveolar fluid clearance, suggesting that lung overinflation may be associated with epithelial dysfunction.

Remifentanil-based sedation to treat noninvasive ventilation failure: a preliminary study.

OBJECTIVE: To assess the feasibility and safety of remifentanil-based sedation during noninvasive ventilation (NIV) in patients with NIV failure. DESIGN AND SETTING: Prospective clinical investigation in a 16-bed intensive care unit of a university hospital in France. PATIENTS: Thirteen patients in NIV failure due to discomfort and/or refusal to continue this ventilatory support: 10 with acute respiratory failure and 3 with acute hypercapnic respiratory failure. INTERVENTION: Patients were administered methylene blue and were sedated (Ramsay scale 2-3) by a continuous perfusion of remifentanil during NIV. Cardiorespiratory and ventilatory parameters, blood gas analysis, and adverse events were prospectively recorded. MEASUREMENTS AND RESULTS: The 13 patients received a total of 125 NIV sessions, totaling 1200 h, of NIV under remifentanil-based sedation (mean remifentanil dose 0.1+/-0.03 microg/kg per minute). Three patients also required propofol. PaO2/FIO2 ratio increased from 134+/-69 to 187+/-43 mmHg after 1 h. In patients with acute respiratory failure respiratory rate decreased from 34+/-12 per minute before remifentanil to 25+/-4 per minute after 1h. In the three patients with acute hypercapnic respiratory failure PaCO2 decreased from 69+/-7 to 42+/-5 mmHg. Four patients required endotracheal intubation without aspiration pneumonia. Twelve of the 13 patients left the ICU. CONCLUSION: This pilot study shows that remifentanil-based sedation is safe and effective in the treatment of NIV failure due to low tolerance.

Lemierre's syndrome and genetic polymorphisms: a case report.

BACKGROUND: Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. CASE PRESENTATION: A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. CONCLUSION: The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology.