Enhanced endoplasmic reticulum RyR1 receptor phosphorylation leads to diaphragmatic dysfunction in septic rats / 南方医科大学学报

OBJECTIVE@#To explore the role of endoplasmic reticulum ryanodine receptor 1 (RyR1) expression and phosphorylation in sepsis- induced diaphragm dysfunction.@*METHODS@#Thirty SPF male SD rats were randomized equally into 5 groups, including a sham-operated group, 3 sepsis model groups observed at 6, 12, or 24 h following cecal ligation and perforation (CLP; CLP-6h, CLP-12h, and CLP-24h groups, respectively), and a CLP-24h group with a single intraperitoneal injection of KN- 93 immediately after the operation (CLP-24h+KN-93 group). At the indicated time points, diaphragm samples were collected for measurement of compound muscle action potential (CMAP), fatigue index of the isolated diaphragm and fitted frequencycontraction curves. The protein expression levels of CaMK Ⅱ, RyR1 and P-RyR1 in the diaphragm were detected using Western blotting.@*RESULTS@#In the rat models of sepsis, the amplitude of diaphragm CMAP decreased and its duration increased with time following CLP, and the changes were the most obvious at 24 h and significantly attenuated by KN-93 treatment (P < 0.05). The diaphragm fatigue index increased progressively following CLP (P < 0.05) irrespective of KN- 93 treatment (P>0.05). The frequency-contraction curve of the diaphragm muscle decreased progressively following CLP, and was significantly lower in CLP-24 h group than in CLP-24 h+KN-93 group (P < 0.05). Compared with that in the sham-operated group, RyR1 expression level in the diaphragm was significantly lowered at 24 h (P < 0.05) but not at 6 or 12 following CLP, irrespective of KN-93 treatment; The expression level of P-RyR1 increased gradually with time after CLP, and was significantly lowered by KN-93 treatment at 24 h following CLP (P < 0.05). The expression level of CaMKⅡ increased significantly at 24 h following CLP, and was obviously lowered by KN-93 treatment (P < 0.05).@*CONCLUSION@#Sepsis causes diaphragmatic dysfunction by enhancing CaMK Ⅱ expression and RyR1 receptor phosphorylation in the endoplasmic reticulum of the diaphragm.

Progress on monitoring technology and assessment indices of pediatric ventilator-induced diaphragm dysfunction / 中国小儿急救医学

Mechanical ventilation is becoming more and more common in clinical practice.It certainly helps patients to overcome the respiratory failure in children, but in the meantime, also lead to ventilator-induced diaphragm dysfunction(VIDD). VIDD is common in mechanical ventilation patients and are associated with prolonged duration of mechanical ventilation, difficult weaning, pulmonary infection and the mortality.With the development of clinical medical technology, more and more convenient devices are applied to monitor diaphragm function.This review expounded the latest monitoring technology and assessment indices of VIDD, including pressure-generating capacity, imaging examination and diaphragm electrical activity.

Effect of respiratory mechanics-guided sedation strategy on diaphragm function in mechanical ventilated patients with chronic obstructive pulmonary disease / 中华危重病急救医学

Objective:To investigate the effects of respiratory mechanics-guided sedation strategy on diaphragm function in chronic obstructive pulmonary disease (COPD) patients treated with mechanical ventilation (MV).Methods:A prospective study was conducted. Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) received invasive MV who were admitted to the Affiliated Huxi Hospital of Jining Medical University from May 2020 to May 2021 were enrolled. The patients were divided into observational group and control group by random number table method. All patients were intubated for MV, and received bronchodilators, glucocorticoid, anti-infectives, expectorant, nutritional support, analgesia and sedation. The sedatives were dexmedetomidine combined with propofol, and the analgesics were sufentanil in both groups. Respiratory mechanics monitoring was performed every 6 hours in the observational group, and the depth of sedation was adjusted according to the parameters of respiratory mechanics: when airway resistance (Raw) > 20 cmH 2O·L -1·s -1, deep sedation was given to maintain Richmond agitation-sedation scale (RASS) ≤ -3; when the Raw was 10-20 cmH 2O·L -1·s -1, the initial depth of sedation maintained to reach the RASS score of -2-0; when Raw < 10 cmH 2O·L -1·s -1, withdrawn the sedation, or given light sedation, and maintained the RASS score of -2-0. While the control group received light sedation. The patients' diaphragmatic excursions (DE) was measured by bedside ultrasound, tidal volume (VT) and respiratory rate (RR) were recorded, and the diaphragmatic rapid shallow breathing index (D-RSBI, D-RSBI = RR/DE) and diaphragmatic excursion efficiency (DEE, DEE = VT/DE) were calculated. The differences in DE, D-RSBI, and DEE before and 3 days and 5 days of treatment between the two groups were compared. The difference in the RASS score within 3 days of sedation between the two groups was compared. The differences in the duration of MV and 28-day mortality between the two groups were compared. Results:A total of 96 patients were selected. Six patients were excluded due to delirium or the duration of MV shorter than 3 days. Finally, 90 patients were enrolled, with 46 in the observational group, and 44 in the control group. There were no statistically significant differences in DE, D-RSBI or DEE before treatment between the two groups. After treatment, D-RSBI in both groups was gradually decreased, and DEE was gradually increased with time. The D-RSBI at 3 days and 5 days of treatment in the observational group were significantly lower than those in the control group (times·min -1·mm -1: 1.73±0.48 vs. 1.96±0.35 at 3 days, 1.45±0.64 vs. 1.72±0.40 at 5 days, both P < 0.05), and DEE were significantly higher than those in the control group (mL/mm: 19.7±4.3 vs. 17.1±3.9 at 3 days, 25.8±5.6 vs. 22.9±5.4 at 5 days, both P < 0.05). There was no significant difference in DE at all time points between the two groups. The RASS scores within 2 hours of sedation in the observational group were significantly lower than those in the control group (1 day: -3.78±0.92 vs. -2.34±0.68, 2 days: -2.87±1.04 vs. -2.43±0.79, both P < 0.05), while no statistical difference at 3 days was found between the two groups. The duration of MV in the observational group was significantly shorter than that in the control group (days: 5.78±2.01 vs. 6.84±2.27, P < 0.05). One patient died in each of the control group and the observational group, and there was no significant difference in the 28-day mortality between the two groups (2.3% vs. 2.2%, P > 0.05). Conclusion:For AECOPD patients undergoing MV, respiratory mechanics-guided sedation strategy can reduce D-RSBI, increase DEE, shorten the duration of MV, and have a certain protective effect on the diaphragm.

Effect of early external diaphragm pacing on patients with mechanical ventilation / 中华急诊医学杂志

Objective:To investigate the effect of early external diaphragm pacing on the diaphragm function and prognosis of patients with mechanical ventilation.Methods:A total of 47 patients receiving invasive mechanical ventilation in the Emergency Intensive Care Unit of Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) from October 2019 to July 2021 were selected and randomly divided into the treatment group ( n=23) and control group ( n=24). The patients in the control group received routine clinical treatment. On this basis, the treatment group received external diaphragm pacing treatment every day from the third day of mechanical ventilation until weaning, and was followed up to 30 days after discharge. The diaphragm thickness, diaphragm excursion, diaphragm thickening fraction, mechanical ventilation time, number of weaning failures, length of hospital stay and death toll were compared between the two groups. Results:Compared with the control group, the diaphragm thickness [(0.21±0.05) cm vs. (0.16±0.05) cm], diaphragm excursion [(1.38±0.37) cm vs. (1.11±0.48) cm], and diaphragm thickening fraction [26% (19%, 32%) vs. 18.5% (10.25%, 20%)] in the treatment group increased significantly (all P<0.05). The mechanical ventilation time was shorter in the treatment group [10 (7, 15) d vs. 13 (10.25, 19) d], and the difference was statistically significant ( P<0.05). There were no significant differences in the number of weaning failures (7 vs. 9), length of hospital stay [22 (15 , 30) d vs.. 24 (17.25, 34.25) d] and deaths (8 vs. 8) (all P>0.05). Conclusions:Early application of external diaphragm pacing can improve the diaphragm function of patients with mechanical ventilation, delay the decline in diaphragm function, increase diaphragm excursion and diaphragm thickening fraction, and shorten the mechanical ventilation time.

Influence and clinical application of acupuncture therapy on weaning from mechanical ventilation / 国际中医中药杂志

The use of mechanical ventilation is more common in the diagnosis and treatment of clinical critically ill patients. However, in the process of mechanical ventilation, it may be difficult to withdraw from the machine due to various factors other than the primary disease. Among them, intra-abdominal hypertension, accumulation of analgesic and sedative drugs, and weakness of diaphragmatic function are common causes of difficulty in weaning. Acupuncture has obvious efficacy in regulating gastrointestinal function, exerting analgesic and sedative effect and improving muscle weakness. Acupuncture intervention can optimize the scheme of mechanical ventilation weaning, and improve the success rate by correcting different concurrent factors.

The protective effect of external diaphragm pacing on ventilator-induced diaphragm dysfunction of rabbits and its mechanism / 中华急诊医学杂志

Objective:To investigate the protective effect of external diaphragm pacing on the prevention of ventilator-induced diaphragm dysfunction (VIDD) in rabbits and its mechanism.Methods:Eighty-five New Zealand white rabbits were randomly (random number) divided into the blank control group (BC, n=5), spontaneous breathing group (SB, n=20), volume control ventilation group (VC, n=20), external diaphragm pacing group (EDP, n=20), external diaphragm pacing and volume control ventilation group (EDP+ VC, n=20). After successful modeling, the rabbits in each group were treated accordingly except for the BC group. Rabbitss in the BC group were not mechanically ventilated, and the diaphragm was removed immediately after anesthetizing. Whole diaphragms of 5 rabbits per time point per other group were also collected after anesthesia at post treatment hour (PTH) 6 and on post treatment day (PTD) 1, 3, and 7. Diaphragm weight/body weight and diaphragm isometric contractile force of each group were measured. The pathological changes of diaphragmatic tissues were observed by HE staining. The protein expressions of Cyt c, RyR1, caspase-3, and p-mTORC1 were measured by Western blot. Repeated measures analysis of variance was used for the comparison between multiple groups of variables at different time points, and LSD- t test was used for the further comparison between two groups at the same time point, a P<0.05 was considered statistically significant. Results:Compared with the BC group, the VC group showed diaphragmatic pathological changes conformed to VIDD: DW/BW was decreased obviously; HE staining revealed obvious changes in diaphragmatic tissue; Diaphragmatic contractility was also significantly decreased; The expression of Cyt c and caspase-3 were increased while the expression of RyR1 and p-mTORC1 were decreased gradually with the extension of treatment time ( P<0.05). Compared the EDP+VC group with the VC group, with the extension of treatment time, DW, DW/BW, pathological damages and diaphragmatic contractility were improved [PTD 1: (0.80±0.05)kg vs (0.56±0.04) kg, PTD 3: (1.06±0.05) kg vs (0.47±0.03) kg, PTD 7: (1.24±0.10) kg vs (0.39±0.07) kg, all P<0.05; PTD 1: (2.05±0.54) vs (1.86±0.72), PTD 3: (2.19±0.61) vs (1.74±0.40), PTD 7: (2.46±0.62) vs (1.53±0.85), all P<0.05; PTD 1: (2.39±0.42) N/cm 2vs (1.91±0.25) N/cm 2, PTD 3: (2.57±0.62) N/cm 2vs (1.72±0.50) N/cm 2, PTD 7: (2.77±0.55) N/cm 2vs (1.54±0.33) N/cm 2, all P<0.05]. The expression of Cyt c and caspase-3 were decreased while the expression of RyR1 and p-mTORC1 were increased gradually in the EDP+VC group ( P<0.05). Conclusions:External diaphragm pacer plays a protective role in ventilator-induced diaphragm dysfunction, which can inhibit mitochondrial damage, reduce oxidative damage, and mitigate diaphragmatic atrophy and injury.

Influences of different mechanical ventilation modes on ventilator-induced diaphragm dysfunction / 实用医学杂志

Objective To investigate the influences of different mechanical ventilation modes on ventilator?induced diaphragm dysfunction (VIDD). Methods The patients received invasive mechanical ventilation in our ICU after lower abdomen surgery were enrolled into 3 groups according to different ventilation modes. The data of the 3 groups were analyzed. According to the offline results, patients were divided into two groups, the success of weaning as the dependent variable, the clinical indicators with statistical significance as the independent variable, the Logistic regression analysis was performed to analyze the ventilator weaning. Results The mechanical ventilation time, 48 h reintubation rate and the length of ICU stay in the A/C mode group were significantly higher than those in the SIMV mode group and the PSV mode group. The weaning success rate in the A/C mode group was significantly lower than that in the SIMV mode group and the PSV mode group, with significant difference (P<0.05). Weaning success group and weaning failure group had significant differences in the proportion of three ventilation modes (P < 0.05). With weaning as dependent variable, APACHE Ⅱ score, ALB and ventilation mode as independent variables, logistic regression analysis was performed using the enter method. APACHE Ⅱ and ventilation mode were independent influencing factors for weaning. Conclusion Compared with the A/C mode, the SIMV mode and the PSV mode have less influence on VIDD and high weaning success rate in the mechanical ventilation process of patients post?lower abdomen surgery. No significant difference was found between the SIMV mode and the PSV mode in their influence on weaning.

Guiding significance of diaphragm function evaluation in ventilation weaning / 中华危重病急救医学

Diaphragm dysfunction is common in clinical work, which is a frequently important cause of ventilation weaning failure ignored by clinicians. Assessing diaphragmatic function while weaning helps early detection and prevention of weaning failure, so as to improve the clinical outcome of patients on mechanical ventilation (MV). Reviewing studies of diaphragmatic function evaluation in weaning, we can find that assessing diaphragmatic function during weaning can help guide weaning. Weaning predictors including pressure index, electrophysiological index and morphological index, among which bedside ultrasound as a morphological index is widely used in intensive care unit (ICU), which is simple, non-invasive, and easy to operate. It is also accurate in the assessment of diaphragmatic function and guidance on weaning, which is worthy of promotion and application.