Effects of acute phase intensive electrical muscle stimulation in COVID-19 patients requiring invasive mechanical ventilation: an observational case-control study.

We investigated the effects of acute-phase intensive electrical muscle stimulation (EMS) on physical function in COVID-19 patients with respiratory failure requiring invasive mechanical ventilation (IMV) in the intensive care unit (ICU). Consecutive COVID-19 patients requiring IMV admitted to a university hospital ICU between January and April 2022 (EMS therapy group) or between March and September 2021 (age-matched historical control group) were included in this retrospective observational case-control study. EMS was applied to both upper and lower limb muscles for up to 2 weeks in the EMS therapy group. The study population consisted of 16 patients undergoing EMS therapy and 16 age-matched historical controls (median age, 71 years; 81.2% male). The mean period until initiation of EMS therapy after ICU admission was 3.2 ± 1.4 days. The EMS therapy group completed a mean of 6.2 ± 3.7 EMS sessions, and no adverse events occurred. There were no significant differences between the two groups in Medical Research Council sum score (51 vs. 53 points, respectively; P = 0.439) or ICU mobility scale at ICU discharge. Addition of upper and lower limb muscle EMS therapy to an early rehabilitation program did not result in improved physical function at ICU discharge in severe COVID-19 patients.

Physical function and mental health trajectories in COVID-19 patients following invasive mechanical ventilation: a prospective observational study.

This prospective observational cohort study was performed to investigate the physical function and mental health trajectories of novel coronavirus disease 2019 (COVID-19) patients requiring invasive mechanical ventilation (IMV) after discharge from the intensive care unit (ICU). The study population consisted of 64 patients (median age, 60 years; 85.9% male; median IMV duration, 9 days). At ICU discharge, 28.1% of the patients had Medical Research Council (MRC) sum score < 48 points, and prolonged IMV was significantly associated with lower MRC sum score and handgrip strength. Symptoms were similar between groups at ICU discharge, and the symptoms most commonly reported as moderate-to-severe were impaired well-being (52%), anxiety (43%), tiredness (41%), and depression (35%). Although muscle strength and mobility status were significantly improved after ICU discharge, Edmonton Symptom Assessment System score did not improve significantly in the prolonged IMV group. EuroQol five-dimension five-level summary index was significantly lower in the prolonged than short IMV group at 6 months after ICU discharge. We found substantial negative physical function and mental health consequences in the majority of surviving COVID-19 patients requiring IMV, with prolonged period of IMV showing greater negative effects not only immediately but also at 6 months after discharge from the ICU.

Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice.

Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED50) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED50 values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED50 values of both anesthetics. After injection of a dose two-fold the ED50 value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.

Clinical impact of visually assessed right ventricular dysfunction in patients with septic shock.

We retrospectively analyzed data from the Medical Information Mart for Intensive Care-III critical care database to determine whether visually-assessed right ventricular (RV) dysfunction was associated with clinical outcomes in septic shock patients. Associations between visually-assessed RV dysfunction by echocardiography and in-hospital mortality, lethal arrhythmia, and hemodynamic indicators to determine the prognostic value of RV dysfunction in patients with septic shock were analyzed. Propensity score analysis showed RV dysfunction was associated with increased risk of in-hospital death in patients with septic shock (adjusted odds ratio [OR] 2.15; 95% confidence interval [CI] 1.99-2.32; P < 0.001). In multivariate logistic regression analysis, RV dysfunction was associated with in-hospital death (OR 2.19; 95% CI 1.91-2.53; P < 0.001), lethal arrhythmia (OR 2.19; 95% CI 1.34-3.57; P < 0.001), and tendency for increased blood lactate levels (OR 1.31; 95% CI 1.14-1.50; P < 0.001) independent of left ventricular (LV) dysfunction. RV dysfunction was associated with lower cardiac output, pulmonary artery pressure index, and RV stroke work index. In patients with septic shock, visually-assessed RV dysfunction was associated with in-hospital mortality, lethal arrhythmia, and circulatory insufficiency independent of LV dysfunction. Visual assessment of RV dysfunction using echocardiography might help to identify the short-term prognosis of patients with septic shock by reflecting hemodynamic status.

The protective effect of tight-fitting powered air-purifying respirators during chest compressions.

BACKGROUND: Airborne personal protective equipment is required for healthcare workers when performing aerosol-generating procedures on patients with infectious diseases. Chest compressions, one of the main components of cardiopulmonary resuscitation, require intense and dynamic movements of the upper body. We aimed to investigate the protective effect of tight-fitting powered air-purifying respirators (PAPRs) during chest compressions. METHODS: This single-center simulation study was performed from February 2021 to March 2021. The simulated workplace protection factor (SWPF) is the concentration ratio of ambient particles and particles inside the PAPR mask; this value indicates the level of protection provided by a respirator when subjected to a simulated work environment. Participants performed continuous chest compressions three times for 2 min each time, with a 4-min break between each session. We measured the SWPF of the tight-fitting PAPR during chest compression in real-time mode. The primary outcome was the ratio of any failure of protection (SWPF <500) during the chest compression sessions. RESULTS: Fifty-four participants completed the simulation. Overall, 78% (n = 42) of the participants failed (the measured SWPF value was less than 500) at least one of the three sessions of chest compressions. The median value and interquartile range of the SWPF was 4304 (685-16,191). There were no reports of slipping down of the respirator or mechanical failure during chest compressions. CONCLUSIONS: Although the median SWPF value was high during chest compressions, the tight-fitting PAPR did not provide adequate protection.

Failure of non-invasive respiratory support after 6 hours from initiation is associated with ICU mortality.

A previous study has shown that late failure (> 48 hours) of high-flow nasal cannula (HFNC) was associated with intensive care unit (ICU) mortality. The aim of this study was to investigate whether failure of non-invasive respiratory support, including HFNC and non-invasive positive pressure ventilation (NPPV), was also associated with the risk of mortality even if it occurs in the earlier phase. We retrospectively analyzed 59 intubated patients for acute respiratory failure due to lung diseases between April 2014 and June 2018. We divided the patients into 2 groups according to the time from starting non-invasive ventilatory support until their intubation: ≤ 6 hours failure and > 6 hours failure group. We evaluated the differences in the ICU mortality between these two groups. The multivariate logistic regression analysis showed the highest mortality in the > 6 hours failure group as compared to the ≤ 6 hours failure group, with a statistically significant difference (p < 0.01). It was also associated with a statistically significant increased 30-day mortality and decreased ventilator weaning rate. The ICU mortality in patients with acute respiratory failure caused by lung diseases was increased if the time until failure of HFNC and NPPV was more than 6 hours.

A case of reexpansion pulmonary edema and acute pulmonary thromboembolism associated with diffuse large B-cell lymphoma treated with venovenous extracorporeal membrane oxygenation.

A 37-year-old man diagnosed with diffuse large B-cell lymphoma two weeks previously, visited our emergency department with sudden dyspnea. He had a severe respiratory failure with saturated percutaneous oxygen at 80% (room air). Chest radiography showed a large amount of left pleural effusion. After 1000 mL of the effusion was urgently drained, reexpansion pulmonary edema (RPE) occurred. Despite ventilator management, oxygenation did not improve and venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated in the intensive care unit. The next day, contrast-enhanced computed tomography showed a massive thrombus in the right pulmonary artery, at this point the presence of pulmonary thromboembolism (PTE) was revealed. Fortunately, the patient's condition gradually improved with anticoagulant therapy and VV-ECMO support. VV-ECMO was successfully discontinued on day 4, and chemotherapy was initiated on day 8. We speculated the following mechanism in this case: blood flow to the right lung significantly reduced due to acute massive PTE, and blood flow to the left lung correspondingly increased, which could have caused RPE in the left lung. Therefore, our observations suggest that drainage of pleural effusion when contralateral blood flow is impaired due to acute PTE may increase the risk of RPE. .

JM-1232(-) and propofol, a new combination of hypnotics with short-acting and non-cumulative preferable properties.

Drug interactions are significant in anesthesiology because drug combinations can potentially possess novel properties. The pharmacological advantages of a new combination of the benzodiazepine receptor agonist JM-1232(-) and propofol were investigated in mice. Male adult mice were administered JM-1232(-) or propofol or combinations of the two drugs intravenously. Loss of the righting reflex was evaluated as achieving hypnosis, and the time until recovery of the reflex was measured as hypnosis time. After determining the ED50, doses double and triple the ED50 of propofol were injected with JM-1232(-) to compare hypnosis time. The injections were repeated four times, and the hypnosis times were compared. Flumazenil was administered separately immediately after the last dose was injected. The ED50 values ([95% confidence interval]) for hypnosis were 3.76 [3.36-4.10] for JM-1232(-) and 9.88 [8.03-11.58] mg kg-1 for propofol. Co-administration of 0.5 and 1 mg kg-1 JM-1232(-) reduced the ED50 values of propofol to 1.76 [1.21-2.51] and 1.00 [0.46-1.86] mg kg-1, respectively. The drug combination for hypnosis produced a supra-additive interaction. Hypnosis time was significantly shorter in the groups given the mixtures compared to each hypnotic administered alone. After repeated injections, hypnosis time with the mixtures showed smaller prolongation than that with the hypnotic alone. Flumazenil completely restored the recovery time after anesthesia. The combination of JM-1232(-) and propofol showed a supra-additive interaction, and the reduced hypnotic dose contributed to a faster recovery even after multiple injections.

[Preservation of the Spinal Perfusion Artery during Descending Thoracic and Thoracoabdominal Aortic Surgery].

This is a 3-case report of successful descending thoracic and thoracoabdominal aortic surgery by preserving the spinal perfusion artery (SPA) identified preoperatively. In Case 1, an 85-year-old woman, computed tomography (CT) showed Crawford type Ⅴ thoracoabdominal aortic aneurysm (TAAA:60 mm) and a SPA originated from L2. In Case 2, a 76-year-old man, CT revealed type Ⅳ TAAA( 58 mm) and a SPA originated from Th11. In Case 3, a 74-year-old man, CT detected an infectious pseudoaneurysm(44 mm) in the descending thoracic aorta with 2 SPAs originating from Th10 and L2. The ranges of graft replacement were Th7-Th12, Th12-L4, and Th8-Th10, respectively, while preserving all SPAs. All patients recovered well without postoperative neurological deficits. Although the protective effect of the SPA preservation against the spinal cord ischemia is still controversial, preoperative identification of the SPA was useful for planning a surgical strategy for descending thoracic and thoracoabdominal aortic repair surgery.

Relative bradycardia as a clinical feature in patients with coronavirus disease 2019 (COVID-19): A report of two cases.

We treated two patients with COVID-19 pneumonia requiring mechanical ventilation. Case 1 was a 73-year-old Japanese man. Computed tomography (CT) revealed ground-glass opacities in both lungs. He had severe respiratory failure with a partial pressure of oxygen in arterial blood/fraction of inspiratory oxygen ratio (P/F ratio) of 203. Electrocardiogram showed a heart rate (HR) of 56 beats/min, slight ST depression in leads II, III, and aVF, and mild saddle-back type ST elevation in leads V1 and V2. High-sensitivity cardiac troponin T (cTnT) level was slightly elevated. Despite a high fever and hypoxemia, his HR remained within 50-70 beats/min. Case 2 was a 52-year-old Japanese woman. CT revealed ground-glass opacities in the lower left lung. Electrocardiogram showed a HR of only 81 beats/min, despite a body temperature of 39.2 °C, slight ST depression in leads V4, V5, V6, and a prominent U wave in multiple leads. She had an elevated cTnT and a P/F ratio of 165. Despite a high fever and hypoxemia, her HR remained within 50-70 beats/min. Both patients had a poor compensatory increase in their HR, despite their critical status. Relative bradycardia could be a cardiovascular complication and is an important clinical finding in patients with COVID-19. .

High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial pneumonia: a retrospective observational study.

High-flow nasal cannula (HFNC) oxygen is a therapy that has demonstrated survival benefits in acute respiratory failure (ARF). However, the role of HFNC in ARF due to interstitial pneumonia (IP) is unknown. The aim of this study was to compare the effects of HFNC therapy and non-invasive positive pressure ventilation (NPPV) in ARF due to IP. This retrospective observational study included 32 patients with ARF due to IP who were treated with HFNC (n = 13) or NPPV (n = 19). The clinical characteristics, intubation rate and 30-day mortality were analyzed and compared between the HFNC group and the NPPV group. Predictors of 30-day mortality were evaluated using a logistic regression model. HFNC group showed higher mean arterial blood pressure (median 92 mmHg; HFNC group vs 74 mmHg; NPPV group) and lower APACHEII score (median 22; HFNC group vs 27; NPPV group) than NPPV group. There was no significant difference in the intubation rate at day 30 between the HFNC group and the NPPV group (8% vs 37%: p = 0.069); the mortality rate at 30 days was 23% and 63%, respectively. HFNC therapy was a significant determinant of 30-day mortality in univariate analysis, and was confirmed to be an independent significant determinant of 30-day mortality in multivariate analysis (odds ratio, 0.148; 95% confidence interval, 0.025-0.880; p = 0.036). Our findings suggest that HFNC therapy can be a possible option for respiratory management in ARF due to IP. The results observed here warrant further investigation of HFNC therapy in randomized control trials.

Relationship Between Serum Norepinephrine Levels at ICU Admission and the Risk of ICU-Acquired Delirium: Secondary Analysis of the Melatonin Evaluation of Lowered Inflammation of ICU Trial.

Abnormal secretion of catecholamines is well known to cause delirium. In particular, disturbances of catecholamine balance can cause ICU-acquired delirium. The aim of this study was to evaluate the association between the serum levels of catecholamines and the risk of occurrence of ICU-acquired delirium separately in patients who had/had not received exogenous catecholamines before ICU admission. DESIGN: A secondary analysis of the data of 81 patients enrolled in our previous randomized clinical trial. SETTING: ICU of an academic hospital. PATIENTS: ICU patients in whom the serum levels of catecholamines were measured at ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the association between the serum levels of catecholamines measured at ICU admission and the risk of ICU-acquired delirium separately in patients who had received exogenous catecholamines at ICU admission (Ex[+] group) and those who had not received exogenous catecholamines (Ex[-] group). The serum levels of norepinephrine measured at ICU admission were significantly associated with the risk of ICU-acquired delirium in the Ex(-) group (odds ratio, 2.58; 95% CI, 1.02-6.52; p = 0.046), but not in the Ex(+) group (odds ratio, 1.02; 95% CI, 0.88-1.18; p = 0.823). Furthermore, there was a statistically significant interaction effect between the serum levels of norepinephrine and the use/nonuse of exogenous catecholamines at ICU admission in relation to the risk of occurrence of ICU-acquired delirium (p interaction = 0.017). CONCLUSIONS: The serum levels of norepinephrine measured at admission were associated with the risk of occurrence of ICU-acquired delirium in patients who had not received exogenous catecholamines at ICU admission, whereas no such association was observed in those who had received exogenous catecholamines previously. Thus, the association between the serum levels of catecholamines measured at admission and the risk of ICU-acquired delirium differed between patients who had/had not received exogenous catecholamines at ICU admission.

Fatal airway obstruction due to a ball-valve clot with identical signs of tension pneumothorax.

Endo-tracheal tube obstruction due to an extensive blood clot is a recognized but very rare complication. A ball-valve obstruction in the airway could function as a check valve for the lung and thorax, resulting in tension pneumothorax-like abnormalities. A 47-year-old female patient had undergone implantation of a left ventricular assist device 3 weeks prior. On post-operative day 17, planned thoracentesis was performed for drainage of a pleural effusion. Despite the drainage, the patient's oxygenation did not improve, and emergency tracheal intubation was conducted. Subsequent computed tomography revealed bilateral pneumothorax. Two days later, the patient's trachea was extubated without complication, and a mini-tracheostomy tube was placed. Three hours later, reintubation was conducted due to progressive tachypnea. Although successful intubation was confirmed, ventilation became increasingly difficult and finally impossible. Marked increase in pulmonary artery and central venous pressures suggested progression of the previous tension pneumothorax. After emergency extracorporeal membrane oxygenation was initiated, fiberoptic bronchoscopy revealed the presence of a massive clot and ball-valve obstruction of the endotracheal tube. Two weeks later, the patient died due to severe hypoxic brain damage. Diagnosis of ball valve clot is not simple, but intensivists should consider this rare complication.

Timing of administration of epinephrine predicts the responsiveness to epinephrine in norepinephrine-refractory septic shock: a retrospective study.

BACKGROUND: Currently, the appropriate method of management of patients with refractory septic shock remains unclear. This study aimed to evaluate the factors associated with response to epinephrine in norepinephrine-refractory septic shock. METHODS: A retrospective single-center observational study was performed using data from adult patients (≥ 18 years old) admitted to our emergency and medical intensive care unit (ICU) from January 2014 to December 2017 who had received epinephrine to treat norepinephrine-refractory septic shock. The response was considered positive if there was increase in mean arterial pressure of 10 mmHg or decrease in arterial lactate level 3 h after epinephrine administration. RESULTS: Forty-one patients were included: 24 responders (59%) and 17 non-responders (41%). Responders showed higher rate of survival from shock (92% vs. 18%; P < 0.001), and 28-day survival (83% vs. 18%; P < 0.001). In multivariable analysis, time of epinephrine administration after ICU admission (odds ratio [OR] 0.48; 95% confidence interval [CI] 0.27-0.87; P = 0.011) and SOFA score (OR 0.19; 95% CI 0.04-0.88; P = 0.034) were associated with epinephrine response. Time of epinephrine administration was also significantly associated with survival from shock (OR 0.42; P = 0.005) and 28-day survival (OR 0.14; P = 0.006), while SOFA score did not. Using inverse probability of treatment weighing (IPTW) adjustment of propensity score, epinephrine administration later than 24 h after ICU admission was associated with poor response (OR 0.07; 95% CI 0.02-0.21; P < 0.001). CONCLUSIONS: Early administration of epinephrine after ICU admission (i.e., within 24 h) is associated with better hemodynamic status in patients with refractory septic shock.

Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial.

OBJECTIVES: Occurrence of delirium in the ICU is associated with a longer stay in the ICU. To examine whether the use of ramelteon, a melatonin agonist, can prevent delirium and shorten the duration of ICU stay of critically ill patients. DESIGN: A single-center, triple-blinded, randomized placebo-controlled trial. SETTING: ICU of an academic hospital. PATIENTS: Eligible patients were ICU patients who could take medicines orally or through a nasogastric tube during the first 48 hours of admission. INTERVENTIONS: The intervention group received ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose powder) at 20:00 hours every day until discharge from the ICU. MEASUREMENTS AND MAIN RESULTS: A total of 88 subjects were randomized to the ramelteon group (45 subjects) or the placebo group (43 subjects). As the primary endpoint, there was a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before and after adjustments). As the secondary endpoints, statistically significant decreases in the occurrence rate (24.4% vs 46.5%; p = 0.044) and duration (0.78 vs 1.40 d; p = 0.048) of delirium were observed in the ramelteon group. The nonintubated patients of the ramelteon group showed statistically significantly fewer awakenings per night and a higher proportion of nights without awakenings. CONCLUSIONS: Ramelteon tended to decrease the duration of ICU stay as well as decreased the occurrence rate and duration of delirium statistically significantly.

A novel scoring system for predicting the neurologic prognosis prior to the initiation of induced hypothermia in cases of post-cardiac arrest syndrome: the CAST score.

BACKGROUND: The aim of this study was to develop a scoring system for identifying the post-cardiac arrest syndrome (PCAS) patients with a good potential for recovery prior to the initiation of induced therapeutic hypothermia. METHODS: A multi-center, retrospective, observational study was performed. Data of a total of 151 consecutive adults who underwent induced hypothermia after cardiac arrest (77 learning cases from two hospitals and 74 validation cases from two other hospitals) were analyzed. RESULTS: In the learning set, 8 factors (initial rhythm, witnessed status and time until return of spontaneous circulation, pH, serum lactate, motor score according to the Glasgow Coma Scale (GCS), gray matter attenuation to white matter attenuation ratio (GWR), serum albumin, and hemoglobin) were found to be strongly correlated with the neurological outcomes. A tentative scoring system was created from the learning data using these factors, and the predictive accuracy (sensitivity and specificity) was evaluated in terms of both internal validation (0.85 and 0.84) and external validation (cutoff 50%: 0.95 and 0.90, 30%: 0.87 and 0.98, 15%: 0.67 and 1.00). Finally, using all the data, we established a post-Cardiac Arrest Syndrome for induced Therapeutic hypothermia (CAST) score to predict the neurologic prognosis prior to initiation of induced hypothermia. CONCLUSIONS: The CAST score was developed to predict the neurological outcomes of PCAS patients treated by induced hypothermia. The likelihood of good recovery at 30 days was extremely low in PCAS patients with a CAST score of ≤15%. Prospective validation of the score is needed in the future.