Long-Term Outcomes of Patients with Stroke Predicted by Clinicians to have no Chance of Meaningful Recovery: A Japanese Cohort Study.

BACKGROUND: Little is known about the natural history of comatose patients with brain injury, as in many countries most of these patients die in the context of withdrawal of life-sustaining therapies (WLSTs). The accuracy of predicting recovery that is used to guide goals-of-care decisions is uncertain. We examined long-term outcomes of patients with ischemic or hemorrhagic stroke predicted by experienced clinicians to have no chance of meaningful recovery in Japan, where WLST in patients with isolated neurological disease is uncommon. METHODS: We retrospectively reviewed the medical records of all patients admitted with acute ischemic stroke, intracerebral hemorrhage, or nontraumatic subarachnoid hemorrhage between January 2018 and December 2020 to a neurocritical care unit at Toda Medical Group Asaka Medical Center in Saitama, Japan. We screened for patients who were predicted by the attending physician on postinjury day 1-4 to have no chance of meaningful recovery. Primary outcome measures were disposition at hospital discharge and the ability to follow commands and functional outcomes measured by the Glasgow Outcome Scale-Extended (GOS-E), which was assessed 6 months after injury. RESULTS: From 860 screened patients, we identified 40 patients (14 with acute ischemic stroke, 19 with intracerebral hemorrhage, and 7 with subarachnoid hemorrhage) who were predicted to have no chance of meaningful recovery. Median age was 77 years (interquartile range 64-85), 53% (n = 21) were women, and 80% (n = 32) had no functional deficits prior to hospitalization. Six months after injury, 17 patients were dead, 14 lived in a long-term care hospital, 3 lived at home, 2 lived in a rehabilitation center, and 2 lived in a nursing home. Three patients reliably followed commands, two were in a vegetative state (GOS-E 2), four fully depended on others and required constant assistance (GOS-E 3), one could be left alone independently for 8 h per day but remained dependent (GOS-E 4), and one was independent and able to return to work-like activities (GOS-E 5). CONCLUSIONS: In the absence of WLST, almost half of the patients predicted shortly after the injury to have no chance of meaningful recovery were dead 6 months after the injury. A small minority of patients had good functional recovery, highlighting the need for more accurate neurological prognostication.

Association of Diaphragm Movement During Cough, as Assessed by Ultrasonography, With Extubation Outcome.

BACKGROUND: A cough peak flow (CPF) of < 60 L/min was associated with increased risk of extubation failure after a successful spontaneous breathing trial (SBT). Passive cephalic excursion of the diaphragm (PCED), measured by ultrasonography during cough expiration, was reported to predict CPF in healthy adults. We hypothesized that PCED, diaphragm peak velocity, or both during cough, as measured by ultrasonography, might predict CPF and extubation outcomes in mechanically ventilated patients. This study attempted to identify associations of diaphragm movement during cough, as assessed by ultrasonography with simultaneously measured CPF, and to determine predictive values of ultrasonographic indices for extubation outcomes after a successful SBT. METHODS: In the study, 252 mechanically ventilated subjects with a successful SBT were enrolled in a prospective cohort study. Right hemidiaphragm passive cephalic excursion and peak velocity were measured by ultrasonography during voluntary cough expiration with maximum effort. CPF was measured simultaneously by ultrasonography. RESULTS: A multiple regression model adjusted for age and sex showed a significant association between PCED and CPF (P < .001, adjusted ß coefficient 11.4, 95% CI 8.88-14.0, adjusted R2 = 0.287) and between diaphragm peak velocity and CPF (P < .001, adjusted ß coefficient 1.71, 95% CI 1.91-2.24, adjusted R2 = 0.235). The areas under the curves of PCED, diaphragm peak velocity, and CPF for extubation failure were 0.791 (95% Cl 0.668-0.914), 0.587 (95% Cl 0.426-0.748), and 0.765 (95% Cl 0.609-0.922), respectively. CONCLUSIONS: PCED on ultrasonography was significantly associated with CPF and extubation failure after a successful SBT. Future studies should investigate if this method is applicable for determination of tracheostomy decannulation in stable patients in general wards.

Prevalence and predictors of direct discharge home following hospitalization of patients with serious adverse events managed by the rapid response system in Japan: a multicenter, retrospective, observational study.

AIM: The rapid response system (RRS) is an in-hospital medical safety system. To date, not much is known about patient disposition after RRS activation, especially discharge home. This study aimed to investigate the prevalence, characteristics, and outcomes of patients with adverse events who required RRS activation. METHODS: Retrospective data from the In-Hospital Emergency Registry in Japan collected from April 2016 to November 2020 were eligible for our analysis. We divided patients into Home Discharge, Transfer, and Death groups. The primary outcome was the prevalence of direct discharge home, and independently associated factors were determined using multivariable logistic regression. RESULTS: We enrolled 2,043 patients who met the inclusion criteria. The prevalence of discharge home was 45.7%; 934 patients were included in the Home Discharge group. Age (adjusted odds ratio [AOR] 0.96; 95% confidence interval [CI], 0.95-0.97), malignancy (AOR 0.69; 95% CI, 0.48-0.99), oxygen administration before RRS (AOR 0.49; 95% CI, 0.36-0.66), cerebral performance category score on admission (AOR 0.38; 95% CI, 0.26-0.56), do not attempt resuscitation order before RRS (AOR 0.17; 95% CI, 0.10-0.29), RRS call for respiratory failure (AOR 0.50; 95% CI, 0.34-0.72), RRS call for stroke (AOR 0.12; 95% CI, 0.03-0.37), and intubation (AOR 0.20; 95% CI, 0.12-0.34) were independently negative, and RRS call for anaphylaxis (AOR 15.3; 95% CI, 2.72-86.3) was positively associated with discharge home. CONCLUSION: Less than half of the in-hospital patients under RRS activation could discharge home. Patients' conditions before RRS activation, disorders requiring RRS activation, and intubation were factors that affected direct discharge home.

Role of a rapid response system and code status discussion as determinants of prognosis for critical inpatients: An observational study in a Japanese urban hospital.

ABSTRACT: Rapid response systems (RRS) have been introduced worldwide to reduce unpredicted in-hospital cardiac arrest (IHCA) and in-hospital mortality. The role of advance care planning (ACP) in the management of critical patients has not yet been fully determined in Japan.We retrospectively assessed the characteristics of all inpatients with unpredicted IHCA in our hospital between 2016 and 2018. Yearly changes in the number of RRS activations and the incidence of unpredicted IHCA with or without code status discussion were evaluated from 2014 to 2018. Hospital standardized mortality ratios were assessed from the data reported in the annual reports by the National Hospital Organization.A total of 81 patients (age: 70.9 ±â€Š13.3 years) suffered an unpredicted IHCA and had multiple background diseases, including heart disease (75.3%), chronic kidney disease (25.9%), and postoperative status (cardiovascular surgery, 18.5%). Most of the patients manifested non-shockable rhythms (69.1%); survival to hospital discharge rate was markedly lower than that with shockable rhythms (26.8% vs 72.0%, P < .001). The hospital standardized mortality ratios was maintained nearly constant at approximately 50.0% for 3 consecutive years. The number of cases of RRS activation markedly increased from 75 in 2014 to 274 patients in 2018; conversely, the number of unpredicted IHCA cases was reduced from 40 in 2014 to 18 in 2018 (P < .001). Considering the data obtained in 2014 and 2015 as references, the RRS led to a reduction in the relative risk of unpredicted IHCA from 2016 to 2018 (ie, 0.618, 95% confidence interval 0.453-0.843). The reduction in unpredicted IHCA was attributed partly to the increased number of patients who had discussed the code status, and a significant correlation was observed between these parameters (R2 = 0.992, P < .001). The reduction in the number of patients with end-stage disease, including congestive heart failure and chronic renal failure, paralleled the incidence of unpredicted IHCA.Both RRS and ACP reduced the incidence of unpredicted IHCA; RRS prevents progression to unpredicted IHCA, whereas ACP decreases the number of patients with no code status discussion and thus potentially reducing the patient subgroup progressing to an unpredicted IHCA.

Intravenous administration of nicorandil immediately before percutaneous coronary intervention can prevent slow coronary flow phenomenon.

AIMS: To determine the effect of intravenous administration of nicorandil on slow coronary flow (SCF) phenomenon in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In a preliminary study, 6 mg of nicorandil showed optimal efficacy for vasodilatation without causing significant haemodynamic instability. In the main study, a total of 408 patients were randomly assigned to receive intravenous administration of 6 mg of nicorandil immediately before PCI. The number of patients in the nicorandil group was 206 [acute coronary syndrome (ACS): 47, non-ACS: 159] and that in the control group was 202 (ACS: 61, non-ACS: 141). Nicorandil significantly decreased the incidence of post-procedural SCF phenomenon in both the ACS and non-ACS groups. The rate of target vessel revascularization (TVR) was significantly lower in the nicorandil group than in the control group in ACS patients. CONCLUSION: Our simple procedure prevented SCF phenomenon not only in patients with ACS but also in patients with non-ACS without any adverse effect. Additionally our procedure reduced the rate of TVR in patients with ACS.

4-Hydroxy-2-nonenal induces calcium overload via the generation of reactive oxygen species in isolated rat cardiac myocytes.

BACKGROUND: It has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca(2+) overload. METHODS AND RESULTS: Exposure to HNE for 10 minutes in the presence of ferric nitrilotriacetate induced the production of hydroxyl radical (.OH) in the rat myocardium as assessed by electron spin resonance spectroscopy, and HNE induced the generation of reactive oxygen species (ROS) in a dose-dependent manner as assessed by 2', 7'-dichlorofluorescein diacetate fluorescence. HNE increased intracellular Ca(2+) concentration ([Ca(2+)](i)) as assessed by fura-2 ratio in a dose- and time-dependent manner. After 20 minutes of HNE (400 micromol/L) exposure, hypercontracture was induced in 67% of the cells. Catalase, an antioxidative enzyme that can decompose hydrogen peroxide (H(2)O(2)), significantly attenuated the increase in [Ca(2+)](i) and completely inhibited hypercontracture. Carvedilol, a beta-blocker with potent antioxidant activity, also significantly attenuated the increase in [Ca(2+)](i) and completely inhibited hypercontracture, but propranolol had no effect on either [Ca(2+)](i) increase or hypercontracture. CONCLUSIONS: HNE induces the formation of ROS, especially H(2)O(2) and .OH, in cardiomyocytes and subsequently ROS cause intracellular Ca(2+) overload. HNE formation may play an important role as a mediator of oxidative stress in heart failure.

The ratio of the atrial areas reflects the clinical status of patients with pulmonary arterial hypertension.

PURPOSE: Echocardiography is useful not only for detecting pulmonary hypertension (PH) but also for estimating the severity of PH by evaluating various morphological changes of the heart caused by pressure and volume overload and by ventricular interaction. We investigated whether a novel echocardiographic index, i.e., the ratio of the atrial areas (RA/LA), would be useful for evaluating the clinical status of patients with pulmonary arterial hypertension (PAH) treated with intravenous epoprostenol. METHODS: We introduced epoprostenol therapy for seven PAH patients without severe tricuspid regurgitation. We evaluated clinical criteria indicative of prognosis, for example World Health Organization functional class (WHO-FC), brain natriuretic peptide (BNP) level, echocardiographic indices such as indexed RA area and RA/LA, and hemodynamics before and one year after intravenous epoprostenol therapy. RESULTS: There were significant improvements in both RA/LA (2.5 ± 1.0, 1.3 ± 0.4, P < 0.001) and indexed RA area (22.5 ± 8.9, 14.5 ± 5.8, P < 0.001). The improvement in RA/LA was more sensitive than that in indexed RA area (P < 0.01). Moreover, RA/LA was significantly correlated with WHO-FC (r = 0.50, P < 0.01) and BNP level (r = 0.82, P < 0.01). CONCLUSIONS: RA/LA is useful for evaluating the clinical status of patients with PAH treated with intravenous epoprostenol.

Ultrasonographic Assessment of Passive Cephalic Excursion of Diaphragm During Cough Expiration Predicts Cough Peak Flow in Healthy Adults.

BACKGROUND: Evaluation of cough strength is clinically important, especially for patients with neuromuscular disorders and before extubation of mechanically ventilated patients. The pressure gradient between the airway and thoracoabdominal cavities during the cough expiratory phase generates cough flow and passive cephalic movement of the diaphragm. We hypothesized that passive diaphragmatic cephalic excursion, peak velocity, or both during cough expiration might predict cough peak flow (CPF). This physiologic study investigated associations of CPF with simultaneously measured ultrasonographic indices in healthy adults during the cough expiratory phase. METHODS: 56 healthy adults participated in this study. Right hemidiaphragm excursion and peak velocity were measured with ultrasonography during voluntary cough expiration with maximum effort. CPF was simultaneously measured for all coughs along with the ultrasonographic measurements. A linear regression model was used to determine whether ultrasonographic indices predicted CPF. RESULTS: Simple regression analysis showed significant associations between excursion and CPF in men and women (P < .001, beta coefficient 37.8, 95% CI 10.9-64.7, adjusted R2 = 0.195 for men; P < .001, beta coefficient 46.1, 95% CI 22.3-69.9, adjusted R2 = 0.386 for women). A multiple regression model adjusted for age, height, and sex showed a significant association between CPF and excursion (P < .001, adjusted beta coefficient 38.32, 95% CI 21.20-55.44, adjusted R2 = 0.643). Simple regression analysis showed a significant association between diaphragmatic peak velocity and CPF only in women (P = .004, beta coefficient 5.07, 95% CI 1.81-8.33, adjusted R2 = 0.280 for women). CONCLUSIONS: Passive cephalic excursion of the diaphragm during the cough expiratory phase significantly predicted CPF with maximum cough effort in healthy adults. Future studies should investigate the relationship between CPF and excursion in persons with respiratory and neuromuscular disorders.

Preliminary guideline- and pathophysiology-based protocols for neurocritical care.

BACKGROUND: Because of the complex pathophysiological processes involved, neurocritical care has been driven by anecdotal experience and physician preferences, which has led to care variation worldwide. Standardization of practice has improved outcomes for many of the critical conditions encountered in the intensive care unit. MAIN BODY: In this review article, we introduce preliminary guideline- and pathophysiology-based protocols for (1) prompt shivering management, (2) traumatic brain injury and intracranial pressure management, (3) neurological prognostication after cardiac arrest, (4) delayed cerebral ischemia after subarachnoid hemorrhage, (5) nonconvulsive status epilepticus, and (6) acute or subacute psychosis and seizure. CONCLUSION: These tentative protocols may be useful tools for bedside clinicians who need to provide consistent, standardized care in a dynamic clinical environment. Because most of the contents of presented protocol are not supported by evidence, they should be validated in a prospective controlled study in future. We suggest that these protocols should be regarded as drafts to be tailored to the systems, environments, and clinician preferences in each institution.

Epicardial electrogram of the right ventricular outflow tract in patients with the Brugada syndrome: using the epicardial lead.

OBJECTIVES: We tried to record an epicardial electrogram directly, and we examined local electrograms before and after administration of a class IC anti-arrhythmic drug in patients with the Brugada syndrome. BACKGROUND: Electrical heterogeneity of the epicardium in the right ventricular outflow tract (RVOT) has been thought to be related to the Brugada syndrome. However, an epicardial abnormality has not been demonstrated in patients with the Brugada syndrome. METHODS: In five patients with a Brugada-type electrocardiogram (ECG), local unipolar electrograms were recorded at the epicardium and endocardium of the RVOT. To record the epicardial electrogram directly, we introduced an electrical guidewire into the conus branch (CB) of the right coronary artery. The duration of the local electrogram after termination of the QRS complex (DP) was measured before and after class IC anti-arrhythmic drug administration. The signal-averaged electrocardiogram (SAECG) was also obtained in all patients. RESULTS: A definite DP was observed at the epicardium, but not at the endocardium. After administration of a class IC anti-arrhythmic drug, the DP at the epicardium was prolonged from 38 +/- 10 ms to 67 +/- 24 ms. The late potential corresponding to the DP at the epicardium was observed in all patients on the SAECG. CONCLUSIONS: An epicardial electrogram can be recorded from the CB. Recording from the CB enables identification of an epicardial abnormality in patients with the Brugada syndrome. These abnormal electrograms may be related to a myocardial abnormality in the epicardium of patients with the Brugada syndrome.

Atrial fibrillation and atrial vulnerability in patients with Brugada syndrome.

OBJECTIVES: We sought to study atrial vulnerability in patients with Brugada syndrome. BACKGROUND: Atrial fibrillation (AF) often occurs in patients with Brugada syndrome, but atrial vulnerability in Brugada syndrome has not been evaluated. METHODS: The patient group consisted of 18 patients with Brugada syndrome. The control group consisted of 12 age- and gender-matched subjects who had neither organic heart disease nor AF episodes. The incidence and clinical characteristics of AF were evaluated in all 18 patients with Brugada syndrome, and an electrophysiologic study was performed in all 12 control subjects and in 14 of the 18 patients with Brugada syndrome. The atrial effective refractory period of the right atrium (RA-ERP), intra-atrial conduction time (conduction time from the stimulus at the right atrium to atrial deflection at the distal portion of the coronary sinus), duration of local atrial potential, and repetitive atrial firing (occurrence of two or more premature atrial complexes after atrial stimulation) were studied. RESULTS: Spontaneous AF occurred in 7 of the 18 patients with Brugada syndrome but in none of the control subjects. The RA-ERP was not different between the two groups. The intra-atrial conduction time was increased in the Brugada syndrome group versus the control group (168.4 +/- 17.5 vs. 131.8 +/- 13.0 ms, p < 0.001). The duration of atrial potential at the RA-ERP was prolonged in the Brugada syndrome group versus the control group (80.3 +/- 18.0 vs. 59.3 +/- 9.2 ms, p < 0.001). Repetitive atrial firing was induced in nine patients with Brugada syndrome and in six control subjects. Atrial fibrillation was induced in eight patients with Brugada syndrome but in none of the control subjects. In patients with Brugada syndrome without spontaneous AF, the intra-atrial conduction time and duration of atrial potential were also increased. CONCLUSIONS: Atrial vulnerability is increased in patients with Brugada syndrome. Abnormal atrial conduction may be an electrophysiologic basis for induction of AF in patients with Brugada syndrome.

Morphologically unique feature of recurrent ampulla (takotsubo) cardiomyopathy.

Two similar rare cases of recurrent ampulla (takotsubo) cardiomyopathy, which was induced by physical stress of recurrent rhabdomyolysis in case 1 and aggravation of respiratory disease in case 2, are presented. At the initial admission, both patients had typical ampulla cardiomyopathy, which was indicated by transient left ventricular (LV) apical ballooning, but at the second admission, they both had atypical ampulla cardiomyopathy, as diagnosed by transient basal midventricular ballooning. Electrocardiograms at each admission showed a specific T-wave inversion, which might indicate the region of LV asynergy, and prolongation of the QT interval. In both cases, the plasma level of endogenous catecholamines was high. It is possible that excessive sympathetic stimulation induced by physical stress was the cause of this cardiomyopathy, but the cause of the differences in wall motion abnormalities between the first and second admissions was not identified. Appropriate management and treatment of the underlying disease and determining the mechanisms of recurrent ampulla cardiomyopathy might prevent its recurrence.

Additional effects of bosentan in patients with idiopathic pulmonary arterial hypertension already treated with high-dose epoprostenol.

BACKGROUND: Combination therapy has been proposed in treatment algorithms for idiopathic pulmonary arterial hypertension (IPAH), so the additional effects of bosentan in IPAH patients already treated with high-dose epoprostenol (EPO) was evaluated in the present study. METHODS AND RESULTS: Bosentan (62.5 mg twice daily) was administered to 8 IPAH patients already being treated with high-dose EPO (average dose 99.6+/-43.4 ng . kg(-1) . min(-1)). Hemodynamics were assessed at baseline and at 2 days and then 1 year after the initiation of bosentan. Because a remarkable elevation of mixed venous oxygen saturation was observed at the initiation of bosentan, the dosage of EPO was reduced in 7 patients (from 99.6+/-43.4 to 82.8+/-31.3 ng . kg(-1) . min(-1), p<0.05). There was a significant decrease from the baseline value for systolic pulmonary artery pressure (80.1+/-19.3 to 66.8+/-16.5 mmHg, p<0.05). These effects were maintained for 1 year without progression of PAH in 6 patients whose condition had been stabilized at baseline. CONCLUSIONS: The additional use of bosentan for IPAH patients whose condition has been stabilized by high-dose EPO is safe and effective.

Prevention of catheter-related infections using a closed hub system in patients with pulmonary arterial hypertension.

BACKGROUND: Most of the patients with pulmonary arterial hypertension (PAH) receiving intravenous epoprostenol have experienced catheter-related infections during long-term treatment. Catheter hub was reported to be the most important source of catheter-related infections. To prevent the catheter-related infections, we have introduced a closed hub system and compared the incidence of catheter-related infections with that in patients using a non-closed hub system. METHODS AND RESULTS: We evaluated the results obtained on 24 occasions in 20 patients with PAH between June 1999 and December 2005. On 11 occasions, a non-closed hub system was used and on 13 cases a closed hub system. We classified the catheter-related infection into a catheter-related bloodstream infection (CRBSI) group or a tunnel infection group based on the pathway of bacteria. The CRBSI rate was 0.89 per 1,000 catheter days in the non-closed hub system group vs 0.10 per 1,000 catheter days in the closed hub system group. Kaplan-Meier analysis showed that the risk of CRBSI significantly decreased in the closed hub system group. None of the patients died as a direct consequence of catheter-related infection during the study period. CONCLUSIONS: We successfully prevented CRBSI by using a closed hub system.