Naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation: A retrospective, single-center cohort study.

INTRODUCTION: There are few reports describing the association of naldemedine with defecation in critically ill patients with opioid-induced constipation. The purpose of this study was to determine whether naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation. METHODS: In this retrospective cohort study, patients admitted to the Intensive Care Unit (ICU) without defecation for 48 hours while receiving opioids were eligible for enrollment. The primary endpoint was the time of the first defecation within 96 hours after inclusion. Secondary endpoints included presence of diarrhea, duration of mechanical ventilation, ICU length of stay, ICU mortality, and in-hospital mortality. The Cox proportional hazard regression analysis with time-dependent covariates was used to evaluate the association naldemedine with earlier defecation. RESULTS: A total of 875 patients were enrolled and were divided into 63 patients treated with naldemedine and 812 patients not treated. Defecation was observed in 58.7% of the naldemedine group and 48.8% of the no-naldemedine group during the study (p = 0.150). The naldemedine group had statistically significantly prolonged duration of mechanical ventilation (8.7 days vs 5.5 days, p < 0.001) and ICU length of stay (11.8 days vs 9.2 days, p = 0.001) compared to the no-naldemedine group. However, the administration of naldemedine was significantly associated with earlier defecation [hazard ratio:2.53; 95% confidence interval: 1.71-3.75, p < 0.001]. CONCLUSION: The present study shows that naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation.

Reducing the effect of immortal time bias affects the analysis of prevention of delirium by suvorexant in critically ill patients: A retrospective cohort study.

BACKGROUND: Studies assessing the effect of suvorexant on delirium prevention included patients treated before development of delirium, which can introduce immortal time bias. The objective of the present study was to evaluate the effect of suvorexant on delirium, comparing patients treated before the onset of delirium with patients treated within 72h of admission using the same dataset. METHODS: Data from adult patients admitted to the ICU from August 2018 to July 2021 were retrospectively analyzed. In "any time before" analysis, the incidence of delirium was compared for patients who received suvorexant at any time during their ICU stay (suvorexant) (unless delirium developed before treatment) with patients who either did not receive suvorexant or received suvorexant after development of delirium (control). This design was used in previously published studies. In "within 72h" analysis, the incidence of delirium was compared for patients who received suvorexant within 72 hours of admission (suvorexant) and patients who did not receive suvorexant or received it more than 72 hours after admission (control). Patients who developed delirium during the initial 72 hours were excluded from "within 72h" analysis (N = 799). RESULTS: "Within 72h" analysis included 1,255 patients, and "any time before" analysis included 2,054 patients (of 6599 admissions). The unadjusted hazard ratio of "any time before" analysis was 0.16 and the 95% confidence interval was 0.13-0.21 (p<0.01). The adjusted hazard ratio was 0.21, and the 95% confidence interval was 0.16-0.27 (p<0.01). "Within 72h" analysis had an unadjusted hazard ratio of 0.54 and the 95% confidence interval was 0.36-0.82 (p<0.01). However, this association lost statistical significance after adjustment for potential confounders (adjusted hazard ratio 1.02, 95% confidence interval 0.65-1.59, p = 0.93). CONCLUSION: Reducing the effect of immortal time bias led to a significantly reduced effect of suvorexant for the prevention of delirium.

ARDS Clinical Practice Guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

ARDS clinical practice guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

Respiratory support strategy in adults with acute hypoxemic respiratory failure: a systematic review and network meta-analysis.

INTRODUCTION: Network meta-analyses (NMAs) of respiratory management strategies for acute hypoxemic respiratory failure (AHRF) have been reported, but no previous study has compared noninvasive ventilation (NIV), high-flow nasal oxygen (HFNO), standard oxygenation therapy (SOT), and invasive mechanical ventilation (IMV) for de novo AHRF. Therefore, we conducted an NMA to assess the effectiveness of these four respiratory strategies in patients with de novo AHRF. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. Studies including adults aged ≥18 years with AHRF and RCTs that compared two different oxygenation techniques (SOT, NIV, HFNO, or IMV) were selected. A frequentist-based approach with multivariate random-effects meta-analysis was used. The outcomes were mortality and intubation rates. RESULTS: Among the 14,263 records initially identified, 25 studies (3302 patients) were included. In the analysis of mortality, compared to SOT, NIV (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.61-0.95) reduced mortality; however, IMV (RR, 1.01; 95% CI, 0.57-1.78) and HFNO (RR, 0.89; 95% CI, 0.66-1.20) did not. For assessments of the intubation incidence, compared to SOT, NIV use (RR, 0.63; 95% CI, 0.51-0.79) was associated with a reduction in intubation, but HFNO (RR, 0.82; 95% CI, 0.61-1.11) was not significant. CONCLUSIONS: Our NMA demonstrated that only NIV showed clinical benefits compared with SOT as an initial respiratory strategy for de novo AHRF. Further investigation, especially comparison with HFNO, is warranted. TRIAL REGISTRATION: PROSPERO (registration number: CRD42020213948 , 11/11/2020).

Association between timing of speech and language therapy initiation and outcomes among post-extubation dysphagia patients: a multicenter retrospective cohort study.

BACKGROUND: Post-extubation dysphagia (PED) is recognized as a common complication in the intensive care unit (ICU). Speech and language therapy (SLT) can potentially help improve PED; however, the impact of the timing of SLT initiation on persistent PED has not been well investigated. This study aimed to examine the timing of SLT initiation and its effect on patient outcomes after extubation in the ICU. METHODS: We conducted this multicenter, retrospective, cohort study, collecting data from eight ICUs in Japan. Patients aged ≥ 20 years with orotracheal intubation and mechanical ventilation for longer than 48 h, and those who received SLT due to PED, defined as patients with modified water swallowing test scores of 3 or lower, were included. The primary outcome was dysphagia at hospital discharge, defined as functional oral intake scale score < 5 or death after extubation. Secondary outcomes included dysphagia or death at the seventh, 14th, or 28th day after extubation, aspiration pneumonia, and in-hospital mortality. Associations between the timing of SLT initiation and outcomes were determined using multivariable logistic regression. RESULTS: A total of 272 patients were included. Of them, 82 (30.1%) patients exhibited dysphagia or death at hospital discharge, and their time spans from extubation to SLT initiation were 1.0 days. The primary outcome revealed that every day of delay in SLT initiation post-extubation was associated with dysphagia or death at hospital discharge (adjusted odds ratio (AOR), 1.09; 95% CI, 1.02-1.18). Similarly, secondary outcomes showed associations between this per day delay in SLT initiation and dysphagia or death at the seventh day (AOR, 1.28; 95% CI, 1.05-1.55), 14th day (AOR, 1.34; 95% CI, 1.13-1.58), or 28th day (AOR, 1.21; 95% CI, 1.07-1.36) after extubation and occurrence of aspiration pneumonia (AOR, 1.09; 95% CI, 1.02-1.17), while per day delay in post-extubation SLT initiation did not affect in-hospital mortality (AOR, 1.04; 95% CI, 0.97-1.12). CONCLUSIONS: Delayed initiation of SLT in PED patients was associated with persistent dysphagia or death. Early initiation of SLT may prevent this complication post-extubation. A randomized controlled study is needed to validate these results.

Efficacy of non-invasive and invasive respiratory management strategies in adult patients with acute hypoxaemic respiratory failure: a systematic review and network meta-analysis.

BACKGROUND: Although non-invasive respiratory management strategies have been implemented to avoid intubation, patients with de novo acute hypoxaemic respiratory failure (AHRF) are high risk of treatment failure. In the previous meta-analyses, the effect of non-invasive ventilation was not evaluated according to ventilation modes in those patients. Furthermore, no meta-analyses comparing non-invasive respiratory management strategies with invasive mechanical ventilation (IMV) have been reported. We performed a network meta-analysis to compare the efficacy of non-invasive ventilation according to ventilation modes with high-flow nasal oxygen (HFNO), standard oxygen therapy (SOT), and IMV in adult patients with AHRF. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. Studies including adults with AHRF and randomized controlled trials (RCTs) comparing two different respiratory management strategies (continuous positive airway pressure (CPAP), pressure support ventilation (PSV), HFNO, SOT, or IMV) were reviewed. RESULTS: We included 25 RCTs (3,302 participants: 27 comparisons). Using SOT as the reference, CPAP (risk ratio [RR] 0.55; 95% confidence interval [CI] 0.31-0.95; very low certainty) was associated significantly with a lower risk of mortality. Compared with SOT, PSV (RR 0.81; 95% CI 0.62-1.06; low certainty) and HFNO (RR 0.90; 95% CI 0.65-1.25; very low certainty) were not associated with a significantly lower risk of mortality. Compared with IMV, no non-invasive respiratory management was associated with a significantly lower risk of mortality, although all certainties of evidence were very low. The probability of being best in reducing short-term mortality among all possible interventions was higher for CPAP, followed by PSV and HFNO; IMV and SOT were tied for the worst (surface under the cumulative ranking curve value: 93.2, 65.0, 44.1, 23.9, and 23.9, respectively). CONCLUSIONS: When performing non-invasive ventilation among patients with de novo AHRF, it is important to avoid excessive tidal volume and lung injury. Although pressure support is needed for some of these patients, it should be applied with caution because this may lead to excessive tidal volume and lung injury. Trial registration protocols.io (Protocol integer ID 49375, April 23, 2021). https://doi.org/10.17504/protocols.io.buf7ntrn .

Validity of an under-mattress sensor for objective sleep measurement in critically ill patients: a prospective observational study.

BACKGROUND: Considering the adverse effects of sleep disturbance in critical care settings, accurate assessment could aid therapy; however, methodological inadequacies mean that no viable option is currently available. Research in healthy population has recently shown that a non-wearable sleep measurement device placed under the mattress of the bed could be beneficial in intensive care settings. Therefore, we aimed to validate this device compared with polysomnography (PSG) and to assess how it related to subjective sleep evaluations. METHODS: This observational study measured the sleep of critically ill adult patients. The primary goal was to validate the Nemuri SCAN (NSCAN; Paramount Bed Co., Ltd., Tokyo, Japan) against the reference standard PSG for 24 h. The secondary goal was to evaluate the association between the objective parameters obtained from NSCAN and PSG and the subjective report data obtained using the Richards-Campbell Sleep Questionnaire (RCSQ) for the nighttime. RESULTS: Eleven participants were evaluated. The median of the total sleep time scored by PSG was 456.0 (353.0-517.5) min during the nighttime and 305.0 (186.2-542.5) min during the daytime. PSG over 24 h revealed significant decreases in restorative sleep, with excessive daytime sleep, but with a normal quantity of nighttime sleep. The agreement, sensitivity, and specificity rates (with 95% confidence intervals) for the NSCAN compared with PSG were 68.4% (67.9-69.0%), 90.1% (89.7-90.6%), and 38.7% (37.9-39.7%), respectively. The median RCSQ value when subjectively evaluating nighttime sleep was 68.0 (26.3-83.5); this showed no correlation with the NSCAN sleep parameters, despite a positive correlation with the ratio of the stage N2 isolated or combined with restorative sleep in the PSG assessment. CONCLUSIONS: NSCAN had moderate agreement, high sensitivity, and poor specificity in intensive care settings, which is most likely due to its inability to identify immobile wakefulness often observed in critically ill patients or sleep depth. This remains a barrier to its use in the assessment of subjective sleep quality. TRIAL REGISTRATION: This investigation was part of an interventional trial registered with the University Hospital Medical Information Network Individual Clinical Trials Registry (UMIN000026350, http://www.umin.ac.jp/icdr/index-j.html) on March 1, 2017.

Impact of increased calls to rapid response systems on unplanned ICU admission.

BACKGROUND: Whether hospital bed number and rapid response system (RRS) call rate is associated with the clinical outcomes of patients who have RRS activations is unknown. We test a hypothesis that hospital volume and RRS call rates are associated with the clinical outcomes of patients with RRSs. METHODS: This is a retrospective chart analysis of an existing dataset associated with In-Hospital Emergency Registry in Japan. In the present study, 4818 patients in 24 hospitals from April 2014 to March 2018 were analyzed. Primary outcome variable was an unplanned intensive care unit (ICU) admission after RRS activation. RESULTS: In the primary analysis of the study using a multivariate analysis adjusting potential confounding factors, higher RRS call rate was significantly associated with decreased unplanned ICU admissions (P < 0.0001, Odds ratio [OR] 0.95, 95% confidence interval [CI] 0.92-0.98), but there was no significant association of hospital volume with unplanned ICU admissions (P = 0.44). In the secondary analysis of the study, there was a non-significant trend of increased cardiac arrest on arrival at the location of the RRS provider at large-volume hospitals (P = 0.084, OR 1.16, 95% CI 0.98-1.38). Large-volume hospitals had a significantly higher 1-month mortality rate (P = 0.0040, OR 1.10, 95% CI 1.03-1.18). CONCLUSION: Hospitals with increased RRS call rates had significantly decreased unplanned ICU admission in patients who had RRS activations. Patients who had RRS activations at large-volume hospitals had an increased 1-month mortality rate.

Suvorexant is associated with a low incidence of delirium in critically ill patients: a retrospective cohort study.

BACKGROUND: Benzodiazepine use is a risk factor for the development of delirium in adult intensive care unit (ICU) patients. Suvorexant is an alternative to benzodiazepines to induce sleep, but the incidence of delirium in critically ill patients is unknown. We undertook this retrospective study to investigate the incidence of delirium in patients who receive suvorexant in the ICU. METHODS: This retrospective cohort study was conducted in a closed 12-bed ICU at a tertiary teaching hospital. Patients admitted to the ICU for 72 h or longer between January and June 2015 were evaluated for delirium using the Confusion Assessment Method for the Intensive Care Unit tool. We evaluated the incidence of delirium in patients who received suvorexant and those who did not. To adjust for confounding factors, multivariable logistic regression analysis was conducted. RESULTS: Study subjects included 118 patients, with a median age of 72 years and a median Acute Physiology and Chronic Health Evaluation II score of 18 points. Eighty-two patients (69.5%) were admitted after cardiovascular surgery. In the suvorexant group, there were fewer post-cardiovascular surgical patients and more medical patients. The duration of mechanical ventilation during ICU stay was longer in the suvorexant group, and sedatives and sleep inducers other than suvorexant were used more frequently in the suvorexant group. The incidence of delirium was 43.8% in the suvorexant group and 58.8% in the non-suvorexant group (P = 0.149). After adjustment for risk factors using multivariable logistic regression analysis, suvorexant was associated with a lower incidence of delirium (odds ratio = 0.23, 95% confidence interval: 0.07-0.73; P = 0.012). CONCLUSIONS: Suvorexant was associated with decreased odds of transitioning to delirium in critically ill patients. The use of suvorexant may lower the incidence of delirium in ICU patients. Future prospective studies are warranted.

Interruption of enteral nutrition in the intensive care unit: a single-center survey.

BACKGROUND: Interruption of enteral nutrition (EN) in the intensive care unit (ICU) occurs frequently for various reasons including feeding intolerance and the conduct of diagnostic and therapeutic procedures. However, few studies have investigated the details of EN interruption practices including reasons for and duration of interruptions. There is no standard protocol to minimize EN interruptions. METHODS: This is a retrospective review of 100 patients in the ICU staying more than 72 h and receiving EN in a 12-bed, medical/surgical ICU in a tertiary care center in 2013. Data collected include total time designated for EN; the number of EN interruption episodes; reason for each interruption categorized as diagnostic study, therapeutic intervention, or gastrointestinal (GI) event, and their individual subcategories; duration of each interruption; and the presence of written orders for interruptions. RESULTS: One hundred patients staying in the ICU for at least 72 h and receiving EN were included. There were 567 episodes of EN interruption over a median ICU length of stay of 17.1 (interquartile range 8.0-22.0) days. There were a median of three EN interruption episodes per patient. EN interruption was performed for undetermined reasons (166 episodes, 29%), airway manipulation (103 episodes, 18%), GI events (78 episodes, 14%), and intermittent dialysis (71 episodes, 13%). Median duration of EN interruption in all patients was 5.5 (3.0-10.0) h. The cumulative interruption time corresponds to 19% of the total time designated for EN. Duration of EN interruption varied according to reason, including airway manipulation (9.0 [5.0-21.0] h), tracheostomy (9.5 [7.5-14.0] h), and GI events (6.5 [3.0-14.0] h). The average calorie deficits due to interruptions were 11.5% of daily target calories. Only 60 episodes (12%) had clear written orders for interruption. CONCLUSIONS: Based on this single-center retrospective chart review, interruption of EN in the ICU is frequent, reasons for and duration of interruption varied, and airway procedures are associated with a relatively longer duration of interruption. Documentation and orders were frequently missing. These results warrant development of a protocol for EN interruption.

[Autopsy case of light chain deposition disease presented by nephrotic syndrome].

An eighty-one-year-old male with lower leg edema and proteinuria was diagnosed as having nephrotic syndrome and was hospitalized for a detailed examination. Kidney biopsy and immunostaining revealed nodular glomerulosclerosis and deposition of lambda chains, respectively. Because these findings indicate the occurrence of light chain deposition disease (LCDD), the underlying disease was found to be multiple myeloma BJ-lambda. After the administration of melphalan and prednisolone, followed by further addition of zoledronic acid, the patient's nephrosis remitted. However, renal dysfunction gradually deteriorated further and hemodialysis was instituted. He eventually died of gastrointestinal bleeding and biliary infection. The period of time from the initial diagnosis to death was thirty months. Autopsy revealed pervasive infiltration of plasma cells and light chain deposition in multiple organs. The uncontrollable gastrointestinal bleeding appears to have been caused by light chain deposition in the vascular walls of a bile duct. Although medical treatment for elderly LCDD cases depends on chemotherapy alone, it is difficult to obtain a complete remission with melphalan and prednisolone, according to the literature. Reports on the validities of biological agents, such as bortezomib, are beginning to appear, and accumulation of further therapeutic experience is eagerly awaited.

Effect of pH and addition of salt on the adsorption behavior of lysozyme on gold, silica, and titania surfaces observed by quartz crystal microbalance with dissipation monitoring.

The adsorption behaviors of lysozyme on dentally related Au, SiO2, and TiO2 surfaces were investigated by a quartz crystal microbalance with dissipation monitoring (QCM-D) method. Frequency shifts indicated that while lysozyme (pI 11) was fairly adsorbed on the SiO2 (pI 1.9) surface at both pH 3 and 7, it was adsorbed on TiO2 (pI 6.3) surface only at pH 7. However, adsorption was disturbed by 50 mM NaCl. These results strongly suggested an electrostatic nature of the adsorption behavior. Though a large-scale adsorption of the lysozyme on Au sensor was pH-insensitive, softness of the adlayer as seen from the dissipation profile was pH-dependent, indicating an interaction of another type. With all the surfaces, the small dissipation change indicated a stiff lysozyme adlayer. Results of this study revealed that the controlled electrostatic interaction between the material surface and lysozyme might be a useful method for imparting antibacterial property to the dental materials.