Association between hypomagnesemia and serum lactate levels in patients with sepsis: a retrospective observational study.

BACKGROUND: Sepsis-3 emphasizes the recognition of sepsis-induced cellular metabolic abnormalities, and utilizes serum lactate level as a biomarker of cellular metabolic abnormalities. Magnesium plays an important role as a cofactor in glucose metabolism, although it is not well known that magnesium deficiency causes elevated serum lactate levels. Additionally, it remains unclear how magnesium status affects the role of serum lactate levels as a marker of metabolic abnormalities in sepsis. Thus, this study aimed to investigate the association between serum magnesium and lactate levels in patients with sepsis and explore this relationship from the perspectives of time course and circulatory abnormalities. METHODS: This retrospective observational study of adult patients with sepsis was performed at the 16-bed intensive care unit of Jichi Medical University Hospital between June 2011 and December 2017. The relationship between serum magnesium and lactate levels for 5 days from intensive care unit admission was investigated along the time course. Multivariate logistic regression analysis was performed to evaluate the association between serum magnesium and lactate levels during intensive care unit admission. RESULTS: Among 759 patients included, 105 had hypomagnesemia (magnesium level < 1.6 mg/dL), 558 had normal serum magnesium levels (1.6-2.4 mg/dL), and 96 had hypermagnesemia (magnesium level > 2.4 mg/dL) at intensive care unit admission. From intensive care unit admission to day 5, the hypomagnesemia group had higher serum lactate levels and a higher frequency of lactic acidosis than the normal magnesium level and hypermagnesemia groups (70% vs. 51.6% vs. 50%; P < 0.001). Hypomagnesemia at intensive care unit admission was independently associated with lactic acidosis, i.e., lactic acid level > 2 mmol/L (odds ratio, 2.76; 95% confidence interval, 1.60-4.76; P < 0.001). CONCLUSIONS: Hypomagnesemia was associated with serum lactate levels in the early and post-resuscitation phases of sepsis. Further studies are needed to elucidate whether the magnesium status is associated with sepsis-induced cellular and metabolic abnormalities.

Significance of Persistent Systemic Support in the Clinical Course of Delayed Post-hypoxic Leukoencephalopathy Following Severe Coronavirus Disease 2019.

A 45-year-old woman was hospitalized with severe coronavirus disease 2019 pneumonia. Following cytokine storm-induced multiorgan failure and lethal arrhythmia, the patient developed a sustained coma with flaccid quadriplegia. A cerebrospinal fluid examination excluded infectious and immunogenic encephalopathies, and diffusion-weighted magnetic resonance imaging demonstrated high-intensity areas in the white matter with a cortex-sparing distribution, suggesting delayed post-hypoxic leukoencephalopathy. As a result of intensive cardiopulmonary support for a month, the neurological function gradually recovered. Based on the reversible clinical course noted in this patient, accurate diagnosis and persistent medical approaches are important for the management of coronavirus disease 2019-related delayed post-hypoxic leukoencephalopathy.

Bias and Precision of Continuous P0.1 Measurement by Various Ventilators: A Simulation Study.

BACKGROUND: Most ventilators measure airway occlusion pressure (occlusion P0.1) by occluding the breathing circuit; however, some ventilators can predict P0.1 for each breath without occlusion. Nevertheless, few studies have verified the accuracy of continuous P0.1 measurement. The aim of this study was to evaluate the accuracy of continuous P0.1 measurement compared with that of occlusion methods for various ventilators using a lung simulator. METHODS: A total of 42 breathing patterns were validated using a lung simulator in combination with 7 different inspiratory muscular pressures and 3 different rise rates to simulate normal and obstructed lungs. PB980 and Dräger V500 ventilators were used to obtain occlusion P0.1 measurements. The occlusion maneuver was performed on the ventilator, and a corresponding reference P0.1 was recorded from the ASL5000 breathing simulator simultaneously. Hamilton-C6, Hamilton-G5, and Servo-U ventilators were used to obtain sustained P0.1 measurements (continuous P0.1). The reference P0.1 measured with the simulator was analyzed by using a Bland-Altman plot. RESULTS: The 2 lung mechanical models capable of measuring occlusion P0.1 yielded values equivalent to reference P0.1 (bias and precision values were 0.51 and 1.06, respectively, for the Dräger V500, and were 0.54 and 0.91, respectively, for the PB980). Continuous P0.1 for the Hamilton-C6 was underestimated in both the normal and obstructive models (bias and precision values were -2.13 and 1.91, respectively), whereas continuous P0.1 for the Servo-U was underestimated only in the obstructive model (bias and precision values were -0.86 and 1.76, respectively). Continuous P0.1 for the Hamilton-G5 was mostly similar to but less accurate than occlusion P0.1 (bias and precision values were 1.62 and 2.06, respectively). CONCLUSIONS: The accuracy of continuous P0.1 measurements varies based on the characteristics of the ventilator and should be interpreted by considering the characteristics of each system. Moreover, measurements obtained with an occluded circuit could be desirable for determining the true P0.1.

Closed-loop ventilation.

PURPOSE OF REVIEW: The last 25 years have seen considerable development in modes of closed-loop ventilation and there are now several of them commercially available. They not only offer potential benefits for the individual patient, but may also improve the organization within the intensive care unit (ICU). Clinicians are showing both greater interest and willingness to address the issues of a caregiver shortage and overload of bedside work in the ICU. This article reviews the clinical benefits of using closed-loop ventilation modes, with a focus on control of oxygenation, lung protection, and weaning. RECENT FINDINGS: Closed-loop ventilation modes are able to maintain important physiological variables, such as oxygen saturation measured by pulse oximetry, tidal volume (VT), driving pressure (ΔP), and mechanical power (MP), within target ranges aimed at ensuring continuous lung protection. In addition, these modes adapt the ventilator support to the patient's needs, promoting diaphragm activity and preventing over-assistance. Some studies have shown the potential of these modes to reduce the duration of both weaning and mechanical ventilation. SUMMARY: Recent studies have primarily demonstrated the safety, efficacy, and feasibility of using closed-loop ventilation modes in the ICU and postsurgery patients. Large, multicenter randomized controlled trials are needed to assess their impact on important short- and long-term clinical outcomes, the organization of the ICU, and cost-effectiveness.

Association between hypomagnesemia and coagulopathy in sepsis: a retrospective observational study.

BACKGROUND: Hypomagnesemia reportedly has significant associations with poor clinical outcomes such as increased mortality and septic shock in patients with sepsis. Although the mechanism underlying these outcomes mostly remains unclear, some experimental data suggest that magnesium deficiency could potentiate coagulation activation in sepsis. However, in sepsis, the association between serum magnesium levels and coagulopathy, including disseminated intravascular coagulation (DIC), remains unknown. Thus, we aimed to investigate the relationship between serum magnesium levels and coagulation status and the association between hypomagnesemia and DIC in patients with sepsis. METHODS: This retrospective observational study was conducted at the intensive care unit (ICU) of a university hospital from June 2011 to December 2017. Patients older than 19 years who met the Sepsis-3 definition were included. We categorized patients into three groups according to their serum magnesium levels: hypomagnesemia (< 1.6 mg/dL), normal serum magnesium level (1.6-2.4 mg/dL), and hypermagnesemia (> 2.4 mg/dL). We investigated the association between serum magnesium levels and overt DIC at the time of ICU admission according to the criteria of the International Society on Thrombosis and Haemostasis. RESULTS: Among 753 patients included in this study, 181 had DIC, 105 had hypomagnesemia, 552 had normal serum magnesium levels, and 96 had hypermagnesemia. Patients with hypomagnesemia had a more activated coagulation status indicated by lower platelet counts, lower fibrinogen levels, higher prothrombin time-international normalized ratios, higher thrombin-antithrombin complex, and more frequent DIC than those with normal serum magnesium levels and hypermagnesemia (DIC: 41.9% vs. 20.6% vs. 24.0%, P < 0.001). The coagulation status in patients with hypomagnesemia was more augmented toward suppressed fibrinolysis than that in patients with normal serum magnesium levels and hypermagnesemia. Multivariate logistic regression revealed that hypomagnesemia was independently associated with DIC (odds ratio, 1.69; 95% confidence interval, 1.00-2.84; P = 0.048) after adjusting for several confounding variables. CONCLUSIONS: Patients with hypomagnesemia had a significantly activated coagulation status and suppressed fibrinolysis. Hypomagnesemia was independently associated with DIC in patients with sepsis. Therefore, the treatment of hypomagnesemia may be a potential therapeutic strategy for the treatment of coagulopathy in sepsis.

Correlation between the hysteresis of the pressure-volume curve and the recruitment-to-inflation ratio in patients with coronavirus disease 2019.

BACKGROUND: Since the response to lung recruitment varies greatly among patients receiving mechanical ventilation, lung recruitability should be assessed before recruitment maneuvers. The pressure-volume curve (PV curve) and recruitment-to-inflation ratio (R/I ratio) can be used bedside for evaluating lung recruitability and individualing positive end-expiratory pressure (PEEP). Lung tissue recruitment on computed tomography has been correlated with normalized maximal distance (NMD) of the quasi-static PV curve. NMD is the maximal distance between the inspiratory and expiratory limb of the PV curve normalized to the maximal volume. However, the relationship between the different parameters of hysteresis of the quasi-static PV curve and R/I ratio for recruitability is unknown. METHODS: We analyzed the data of 33 patients with severe coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. Respiratory waveform data were collected from the ventilator using proprietary acquisition software. We examined the relationship of the R/I ratio, quasi-static PV curve items such as NMD, and respiratory system compliance (Crs). RESULTS: The median R/I ratio was 0.90 [interquartile range (IQR), 0.70-1.15] and median NMD was 41.0 [IQR, 37.1-44.1]. The NMD correlated significantly with the R/I ratio (rho = 0.74, P < 0.001). Sub-analysis showed that the NMD and R/I ratio did not correlate with Crs at lower PEEP (- 0.057, P = 0.75; and rho = 0.15, P = 0.41, respectively). On the contrary, the ratio of Crs at higher PEEP to Crs at lower PEEP (Crs ratio (higher/lower)) moderately correlated with NMD and R/I ratio (rho = 0.64, P < 0.001; and rho = 0.67, P < 0.001, respectively). CONCLUSIONS: NMD of the quasi-static PV curve and R/I ratio for recruitability assessment are highly correlated. In addition, NMD and R/I ratio correlated with the Crs ratio (higher/lower). Therefore, NMD and R/I ratio could be potential indicators of recruitability that can be performed at the bedside.

Use of broad-spectrum antimicrobials for more than 72 h and the detection of multidrug-resistant bacteria in Japanese intensive care units: a multicenter retrospective cohort study.

BACKGROUND: Large multicenter studies reporting on the association between the duration of broad-spectrum antimicrobial administration and the detection of multidrug-resistant (MDR) bacteria in the intensive care unit (ICU) are scarce. We evaluated the impact of broad-spectrum antimicrobial therapy for more than 72 h on the detection of MDR bacteria using the data from Japanese patients enrolled in the DIANA study. METHODS: We analyzed the data of ICU patients in the DIANA study (a multicenter international observational cohort study from Japan). Patients who received empirical antimicrobials were divided into a broad-spectrum antimicrobial group and a narrow-spectrum antimicrobial group, based on whether they received broad-spectrum antimicrobials for more or less than 72 h, respectively. Differences in patient characteristics, background of infectious diseases and empirical antimicrobial administration, and outcomes between the two groups were compared using the chi-square tests (Monte Carlo method) for categorical variables and the Mann-Whitney U-test for continuous variables. We also conducted a logistic regression analysis to investigate the factors associated with the detection of new MDR bacteria. RESULTS: A total of 254 patients from 31 Japanese ICUs were included in the analysis, of whom 159 (62.6%) were included in the broad-spectrum antimicrobial group and 95 (37.4%) were included in the narrow-spectrum antimicrobial group. The detection of new MDR bacteria was significantly higher in the broad-spectrum antimicrobial group (11.9% vs. 4.2%, p = 0.042). Logistic regression showed that broad-spectrum antimicrobial continuation for more than 72 h (OR [odds ratio] 3.09, p = 0.047) and cerebrovascular comorbidity on ICU admission (OR 2.91, p = 0.041) were associated with the detection of new MDR bacteria. CONCLUSIONS: Among Japanese ICU patients treated with empirical antimicrobials, broad-spectrum antimicrobial usage for more than 72 h was associated with the increased detection of new MDR bacteria. Antimicrobial stewardship programs in ICUs should discourage the prolonged use of empirical broad-spectrum antimicrobial therapy. Trial registration ClinicalTrials.gov, NCT02920463, Registered 30 September 2016, https://clinicaltrials.gov/ct2/show/NCT02920463.

Upper Arm Muscular Echogenicity Predicts Intensive Care Unit-acquired Weakness in Critically Ill Patients.

Objectives: This retrospective observational study investigated whether the degree of muscular echogenicity in patients admitted to the intensive care unit (ICU) could help with the early detection of ICU-acquired weakness (ICU-AW) and predict physical function at hospital discharge. Methods: Twenty-five patients who were mechanically ventilated for more than 48 h in the ICU were enrolled. We also enrolled 23 outpatients with nonmuscular diseases as the control group. The target sites for measuring muscular echogenicity were the upper arm and lower leg. First, the muscular echogenicity was compared between surviving nonsurgical patients admitted to the ICU and stable outpatients with nonmuscular diseases. Second, we investigated the relationship between muscular echogenicity and clinical features, e.g., the manual muscle test (MMT), Medical Research Council (MRC) sum score, and Functional Independence Measure (FIM). Results: Muscular echogenicity in the upper arm in the ICU group was significantly higher than that in the control group. In the ICU group, the degree of muscular echogenicity of the upper arm was inversely correlated with the MMT of elbow flexion (P=0.006; r=-0.532) and the MRC sum score (P=0.002; r=-0.591). However, muscular echogenicity of the upper arm did not correlate with functional FIM (P=0.100; r=-0.344) at hospital discharge. Conclusions: Critically ill patients can experience pathological muscle weakness associated with increased muscular echogenicity in the upper arm. Additionally, the degree of muscular echogenicity in the upper arm correlated with the MRC sum score and can facilitate early detection of ICU-AW. The relationship between echogenicity and functional outcome at discharge requires elucidation.

Accuracy of two pulse-oximetry measurements for INTELLiVENT-ASV in mechanically ventilated patients: a prospective observational study.

Recently, maintaining a certain oxygen saturation measured by pulse oximetry (SpO2) range in mechanically ventilated patients was recommended; attaching the INTELLiVENT-ASV to ventilators might be beneficial. We evaluated the SpO2 measurement accuracy of a Nihon Kohden and a Masimo monitor compared to actual arterial oxygen saturation (SaO2). SpO2 was simultaneously measured by a Nihon Kohden and Masimo monitor in patients consecutively admitted to a general intensive care unit and mechanically ventilated. Bland-Altman plots were used to compare measured SpO2 with actual SaO2. One hundred mechanically ventilated patients and 1497 arterial blood gas results were reviewed. Mean SaO2 values, Nihon Kohden SpO2 measurements, and Masimo SpO2 measurements were 95.7%, 96.4%, and 96.9%, respectively. The Nihon Kohden SpO2 measurements were less biased than Masimo measurements; their precision was not significantly different. Nihon Kohden and Masimo SpO2 measurements were not significantly different in the "SaO2 < 94%" group (P = 0.083). In the "94% ≤ SaO2 < 98%" and "SaO2 ≥ 98%" groups, there were significant differences between the Nihon Kohden and Masimo SpO2 measurements (P < 0.0001; P = 0.006; respectively). Therefore, when using automatically controlling oxygenation with INTELLiVENT-ASV in mechanically ventilated patients, the Nihon Kohden SpO2 sensor is preferable.Trial registration UMIN000027671. Registered 7 June 2017.

Translation and validation of the Japanese version of the measure of moral distress for healthcare professionals.

OBJECTIVES: Moral distress occurs when professionals cannot carry out what they believe to be ethically appropriate actions because of constraints or barriers. We aimed to assess the validity and reliability of the Japanese translation of the Measure of Moral Distress for Healthcare Professionals (MMD-HP). METHODS: We translated the questionnaire into Japanese according to the instructions of EORTC Quality of Life group translation manual. All physicians and nurses who were directly involved in patient care at nine departments of four tertiary hospitals in Japan were invited to a survey to assess the construct validity, reliability and factor structure. Construct validity was assessed with the relation to the intention to leave the clinical position, and internal consistency was assessed with Cronbach's alpha. Confirmatory factor analysis was conducted. RESULTS: 308 responses were eligible for the analysis. The mean total score of MMD-HP (range, 0-432) was 98.2 (SD, 59.9). The score was higher in those who have or had the intention to leave their clinical role due to moral distress than in those who do not or did not have the intention of leaving (mean 113.7 [SD, 61.3] vs. 86.1 [56.6], t-test p < 0.001). The confirmatory factor analysis and Cronbach's alpha confirmed the validity (chi-square, 661.9; CMIN/df, 2.14; GFI, 0.86; CFI, 0.88; CFI/TLI, 1.02; RMSEA, 0.061 [90%CI, 0.055-0.067]) and reliability (0.91 [95%CI, 0.89-0.92]) of the instrument. CONCLUSIONS: The translated Japanese version of the MMD-HP is a reliable and valid instrument to assess moral distress among physicians and nurses.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.