BackgroundCipepofol is a highly selective gamma-aminobutyric acid A receptor potentiator. As a new sedative drug, detailed studies on its respiratory effects are further needed. The present study aims to investigate the effects of cipepofol on breathing patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients.MethodsIn this one-arm physiological study, cipepofol was initiated at 0.3 mg/kg/h and increased by 0.1 mg/kg/h every 30 min until reaching 0.8 mg/kg/h. Discontinuation criteria were Richmond Agitation and Sedation Scale (RASS) score ≤ −4 or respiratory rate (RR) < 8 breaths/min or pulse oxygen saturation (SpO2) < 90%. The primary outcomes were changes from baseline in respiratory variables [RR, tidal volume (VT), minute ventilation (Vmin), airway occlusion pressure at 100 msec (P0.1), pressure muscle index (PMI), expiratory occlusion pressure (Pocc)] at 30 min after 0.3 mg/kg/h cipepofol infusion. The secondary outcomes included changes in respiratory variables, cardiorespiratory variables, and RASS scores at rates of cipepofol from 0.3 to 0.8 mg/kg/h.Results20 patients were enrolled and all of them completed the cipepofol infusion rate at 0.3 mg/kg/h, achieving RASS score of −2 to +1. For the primary outcomes, there was a significant reduction in VT (390.9, [356.6–511.0] vs. 451.6 [393.5–565.9], p = 0.002), while changes in RR (16.7 ± 2.7 vs. 16.2 ± 3.4, p = 0.465) and Vmin (7.2 ± 1.8 vs. 7.5 ± 1.9, p = 0.154) were not significant. The reductions in P0.1 (p = 0.020), PMI (p = 0.019), and Pocc (p = 0.007) were significant. For secondary outcomes, as the infusion rate of cipepofol increased from 0.3 to 0.8 mg/kg/h, there was a further decrease in VT (p = 0.002) and an increase in RR (p < 0.001), while the change in Vmin (p = 0.430) was not significant. RASS score (p < 0.001) was further decreased.ConclusionCipepofol demonstrates the capability to achieve RASS score −2 to +1 in mechanically ventilated adult patients. The effect of cipepofol on breathing patterns was a decrease in VT, while changes in RR and Vmin were insignificant. The effect on respiratory drive and inspiratory effort significantly reduced P0.1, PMI, and Pocc.Clinical trial registrationClinicalTrials.gov, identifier NCT06287138. https://clinicaltrials.gov/study/NCT06287138

IntroductionIsotonic crystalloids are commonly used for maintaining fluid balance and cerebral perfusion pressure in critical care patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the relatively high concentration of chloride in normal saline (NS) might lead to hyperchloremia or acute kidney injury, comparing with multi-electrolyte solutions (BMES). The aim of the study is to compare the incidence of hyperchloremia in aSAH patients and provide feasibility and safety research for further study.MethodsThis is a pilot study of a single center, randomized, controlled trail. Patients were enrolled randomly to receive BMES or NS for 3 days of ICU stay.ResultsOverall, 87 patients were randomized to receive BMES or NS, 60 patients (30 in each group) were enrolled for final analysis. Within 3 days of randomization, hyperchloremia occurred in 18/30 (60%) patients in the BMES group and 23/30 (76.7%) in the NS group (p = 0.165, relative risk 0.58, 95% CI 0.27–1.28). Incidence of hyperchloremia (BMES 36.7% vs. NS 63.3%, p = 0.039) and hyperchloremic acidosis (BMES 36.7% vs. NS 63.3%, p = 0.039) were decreased on trial day 1. There were no differences on bicarbonate, anion gap, serum creatinine, incidence of acute kidney injury, or length of hospital stay between groups.DiscussionFor patients with aSAH, the use of BMES did not result in a lower risk of hyperchloremia, and also did not increase the incidence of hyponatremia or intracranial hypertension over NS, which warrants further research.

Background. Identifying the causative pathogens of central nervous system infections (CNSIs) is crucial, but the low detection rate of traditional culture methods in cerebrospinal fluid (CSF) has made the pathogenic diagnosis of CNSIs a longstanding challenge. Patients with CNSIs after neurosurgery often overlap with inflammatory and bleeding. Metagenomic next-generation sequencing (mNGS) has shown some benefits in pathogen detection. This study aimed to investigate the diagnostic performance of mNGS in the etiological diagnosis of CNSIs in patients after neurosurgery. Methods. In this prospective observational study, we enrolled patients with suspected CNSIs after neurosurgical operations who were admitted to the intensive care unit of Beijing Tiantan Hospital. All enrolled patients' CSF was tested using mNGS and pathogen culture. According to comprehensive clinical diagnosis, the enrolled patients were divided into CNSIs group and non-CNSIs group to compare the diagnostic efficiency of mNGS and pathogen culture. Results. From December 2021 to March 2023, 139 patients were enrolled while 66 in CNSIs group and 73 in non-CNSIs. The mNGS exceeded culture in the variety and quantity of pathogens detected. The mNGS outperformed traditional pathogen culture in terms of positive percent agreement (63.63%), accuracy (82.01%), and negative predictive value (75.00%), with statistically significant differences (P < 0.05) for traditional pathogen culture. The mNGS also detected bacterial spectrum and antimicrobial resistance genes. Conclusions. Metagenomics has the potential to assist in the diagnosis of patients with CNSIs who have a negative culture.

Background:Cerebral blood flow (CBF) is closely regulated by carbon dioxide (CO2). In patients with aneurysmal subarachnoid hemorrhage (aSAH), abnormal arterial partial pressure of CO2 (PaCO2) might deteriorate brain injuries. Nevertheless, the impact of dynamic PaCO2 fluctuations on neurological outcomes in aSAH patients has not been extensively studied. Our study aimed to investigate the association between dynamic PaCO2 levels and unfavorable neurological outcomes in aSAH patients. Methods:In this retrospective observational study, we consecutively enrolled 159 aSAH patients from December 2019 to July 2021. Arterial blood gas measurements within 10 days after intensive care unit (ICU) admission for each patient were recorded to calculate the time-weighted average (TWA)-PaCO2, an indicator representing the dynamic changes in PaCO2 levels. For the association between TWA-PaCO2 levels and unfavorable neurological outcomes in aSAH patients, multivariable logistic analysis was used to explore TWA-PaCO2 levels as categorical variables, and restricted cubic spline (RCS) was used to explore TWA-PaCO2 levels as continuous variables. Results:In multivariable logistic analysis, after adjusting confounders, when TWA-PaCO2 35-45 mmHg was as a reference, TWA-PaCO2 < 35 mmHg (odds ratio [OR] 2.15, 95 % confidence interval [CI] 0.83-5.55, P = 0.113) and TWA-PaCO2 > 45 mmHg (OR 8.31, 95 % CI 0.72-96.14, P = 0.090) were not independently associated with unfavorable neurological outcomes (modified Rankin score of 3-6). The RCS shows a "U" shape curve between TWA-PaCO2 levels and unfavorable neurological outcomes, with a nonlinear P-value of 0.023. The lowest ORs of unfavorable neurological outcomes were within PaCO2 32.8-38.1 mmHg. Conclusions:Both lower and higher PaCO2 levels are harmful to aSAH patients. PaCO2 in the range of 32.8-38.1 mmHg is associated with lowest unfavorable neurological outcomes.

Introduction Spontaneous hyperventilation (SHV) is common in aneurysmal subarachnoid haemorrhage (aSAH). The reduction in arterial partial pressure of carbon dioxide (PaCO2) may change the brain physiology, such as haemodynamics, oxygenation, metabolism and may lead to secondary brain injury. However, how to correct SHV safely and effectively in patients with aSAH has not been well investigated. The aim of this study is to investigate the efficacy and safety of remifentanil dose titration to correct hyperventilation in aSAH, as well as the effect of changes in PaCO2 on cerebral blood flow (CBF). Methods and analysis This study is a prospective, single-centre, physiological study in patients with aSAH. The patients who were mechanically ventilated and who meet with SHV (tachypnoea combined with PaCO2 <35 mm Hg and pH >7.45) will be enrolled. The remifentanil will be titrated to correct the SHV. The predetermined initial dose of remifentanil is 0.02 μg/kg/min and will be maintained for 30 min, and PaCO2 and CBF will be measured. After that, the dose of remifentanil will be sequentially increased to 0.04, 0.06, and 0.08 μg/kg/min, and the measurements for PaCO2 and CBF will be repeated 30 min after each dose adjustment and will be compared with their baseline values. Ethics and dissemination This study has been approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University (KY 2021-006-02) and has been registered at ClinicalTrials.gov. The results of this study will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT04940273.

Background The aim of the study was to determine whether the combination of Glasgow Coma Scale (GCS) and Pupil responses score (GCSP) with arterial lactate level would be an index to predict the short term prognosis in patients with traumatic brain injury (TBI). Methods A retrospective study was performed enrolling all TBI patients admitted to intensive care unit (ICU) from 2019 to 2020. The demographics, clinical characteristics, and arterial lactate concentration were recorded. The GCSP and arterial blood analysis (ABG) with lactate was tested as soon as the patient was admitted to ICU. The Glasgow Outcome Scale (GOS) after discharge was regarded as the clinical outcome. A new index named GCSP-L was the combination of GCSP and lactate concentration. GCSP-L was the GCSP score (range 1-15) plus the lactate score (range 0-2). The lactate score was defined based on different lactate concentrations. If lactate was below 2 mmol/L, lactate score was 0, which above 5 mmol/L was 2 and between 2 and 5 mmol/L, the score was 1. As the range of GCSP was 1-15, the range of the GCSP-L was 1 to 17. The area under receiver operating characteristic curve (AUC) was calculated to evaluate the predictive ability of GCSP, lactate and GCSP-L. Statistical significance was set when p value < 0.05. Results A total of 192 TBI patients were included in the study. Based on GCSP, mild, moderate, and severe TBI were 13.02, 14.06 and 72.92%, respectively. There were 103 (53.65%) patients with the lactate concentration below 2 mmol/L (1.23 ± 0.37 mmol/l), 63 (32.81%) of the range from 2 to 5 (3.04 ± 2.43 mmol/l) and 26 (13.54%) were above 5 mmol/l (7.70 ± 2.43 mmol/l). The AUC was 0.866 (95% CI 0.827-0.904) for GCSP-L, 0.812 (95% CI 0.765-0.858) for GCSP and 0.629 (95% CI 0.570—0.0.688) for lactate. The AUC of GCSP-L was higher than the other two, GCSP and lactate alone. Conclusions The combination of GCSP and lactate concentration can be used to predict the short term prognosis in TBI patients.

Physical restraints are widely used in hospitalized and critically ill patients, especially in intensive care unit (ICU), to prevent adverse events such as the accidental removal of various monitoring leads, therapeutic tubes, and self-injury or injury to others due to delirium and irritation. The existing restraint measures directly bind the upper limbs of the patients to the hospital bed, which often brings psychological harm to the patients and leads to disuse muscular atrophy. Early rehabilitation therapy can help improve the prognosis of patients,but it is difficult to be widely used in ICU due to being heavily dependent on nursing and rehabilitation physicians. A novel restraint device to facilitate rehabilitation training for critically ill patients was designed by the medical staff from the department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University and obtained the National Utility Model Patent of China (ZL 2020 2 2492749.6). The device is mainly composed of a cross beam and a locking device whose two ends are connected by a rocker arm, an upper limb stopper and an upper body stopper. The upper limb and body restraint provide restrictions on the movement of the head, the upper limb, and the upper body. The angle limiter prevents the patient from pulling out the treatment tube by himself, and at the same time retains the ability to grasp the crossbar and rotate it, and the sliding block further increases the activity space, to meet the exercise of the patient's upper limb muscle strength. Carrying out physical rehabilitation training as early as possible during ICU treatment can relieve the patient's resistance to passive restraint, reduce the incidence of disuse muscle atrophy, eliminate the potential hidden dangers of medical disputes, and ultimately improve the prognosis of patients.

Using artificial dead space to correct hypocapnia or induce hypercapnia is of particular significance for diagnosing and treating specific neurocritical diseases. At present, the above purpose is mainly achieved by adding an extension tube between the Y-type connector of the ventilator and the artificial airway in clinical practice. However, its volume is often fixed and cannot adapt to the individualized diagnosis and treatment in different clinical scenarios. The research group led by Professor Zhou Jianxin from the department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University, has designed an artificial dead cavity with adjustable volume based on years of research in the respiratory field and has been granted a national utility model patent (patent number: ZL 2020 2 0496413.4). The artificial dead chamber is simple in structure, composed of a barrel body, a piston head, and a push-pull rod. By freely adjusting the size of the artificial dead chamber volume, it can accurately regulate the target carbon dioxide, correct the spontaneous hyperventilation, terminate intractable hiccup, and shorten the operation time of asphyxia test in clinical diagnosis of brain death while correcting hypocapnia or inducing hypercapnia. It has the advantages of solid reliability, convenient operation, and low production cost, which significantly facilitates scientific research and clinical diagnosis and treatment.