Factors Underlying the Early Limb Muscle Weakness in Acute Quadriplegic Myopathy Using an Experimental ICU Porcine Model

The basic mechanisms underlying acquired generalized muscle weakness and paralysis in critically ill patients remain poorly understood and may be related to prolonged mechanical ventilation/immobilization (MV) or to other triggering factors such as sepsis, systemic corticosteroid (CS) treatment and administration of neuromuscular blocking agents (NMBA). The present study aims at exploring the relative importance of these factors by using a unique porcine model. Piglets were all exposed to MV together with different combinations of endotoxin-induced sepsis, CS and NMBA for five days. Peroneal motor nerve conduction velocity and amplitude of the compound muscle action potential (CMAP) as well as biceps femoris muscle biopsy specimens were obtained immediately after anesthesia on the first day and at the end of the 5-day experimental period. Results showed that peroneal nerve motor conduction velocity is unaffected whereas the size of the CMAP decreases independently of the type of intervention, in all groups after 5 days. Otherwise, despite a preserved size, muscle fibre specific force (maximum force normalized to cross-sectional area) decreased dramatically for animals exposed to MV in combination with CS or/and sepsis. These results suggest that the rapid declines in CMAP amplitude and in force generation capacity are triggered by independent mechanisms with significant clinical and therapeutic implications

Diaphragm Muscle Weakness in an Experimental Porcine Intensive Care Unit Model

In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

A Many-analysts Approach to the Relation Between Religiosity and Well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β = 0.120). For the second research question, this was the case for 65% of the teams (median reported β = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

Studies of diaphragm fatigue and dysfunction

Diaphragm fatigue and dysfunction are important components of acute and chronic respiratory pump failure. We lack knowledge about the nature of diaphragm fatigue and the pathophysiological and morphological changes that occur in the diaphragm after prolonged mechanical ventilation. This thesis studied two aspects of diaphragm function. Diaphragm contractility and oxidative metabolism were studied during inspiratory resistive loaded breathing (IRB) and hypoxia, and diaphragm contractility, activation and morphology were examined during prolonged mechanical ventilation. Additionally, ultrasonography was evaluated as a quantitative measure of diaphragm function. Methods: Anesthetized piglets ages 4-6 weeks (studies I, II, III) or 2-4 months (studies IV, V) were studied. Diaphragm contractility was evaluated in all studies by measurement of transdiaphragmatic pressure, Pdi achieved by supramaximal phrenic nerve stimulation with transvenous stimulation electrodes. Intracellular high energy phosphates (ATP, phosphocreatine) were measured b y 31 phosphorus nuclear magnetic spectroscopy (NMS) following diaphragm fatigue induced by repetitive phrenic nerve stimulation and IRB (study I), as well as IRB and hypoxia (study II). Ultrasonography measurements of the posterior diaphragm were obtained in die transverse and lateral sagital planes, using 2D and m-modes, and were tested for agreement with measures of contractility before and after evoked diaphragm fatigue (study III). Combined diaphragm EMG, phrenic nerve- diaphragm electroneurogram and Pdi were obtained daily in studies of prolonged, controlled mechanical ventilation and evaluated along with repeated measures of dynamic lung compliance and airway resistance (study IV). Morphology, fiber type proportions and size were studied from diaphragm biopsies obtained from study animals and compared to controls (study V). Results: Spontaneous inspiratory resistive breathing led to respiratory failure (acidosis and hypercarbia) but preserved peripheral diaphragm contractility and oxidative metabolism. The addition of hypoxemia to ERB did result however, in decreased Pdi and signs of inadequate oxidative metabolism (rise in ratio of inorganic phosphate to phosphocreatine). Diaphragm fatigue induced by repetitive phrenic nerve stimulation was associated with a change in ultrasound m-mode measurement of mean inspiratory velocity of the right posterior hemidiaphragm. Prolonged mechanical ventilation and diapluagm inactivity over 5 days resulted in decreased Pdi over frequencies from 20 to 100 Hz and activation as measured by compound muscle action potential amplitude. Nerve conduction and neuromuscular transmission remained in tact. Morphologic signs of muscle adaptation or injury included areas of regeneration, micro-vacuolization and poor histologic staining for m-ATPase, which may be associated with loss of myosin. Conclusions: Acute respiratory failure in anesthetized piglets during spontaneous inspiratory resistive breathing is not caused by diaphragm fatigue due to decreased contractility or inadequate diaphragm oxidative metabolism. Ile addition of severe hypoxemia to inspiratory resistive breathing results, however, in inadequate oxidative metabolism and decreased contractility which may contribute to the respiratory failure seen. Utrasonography can be used to quantify diaphragm function and identify diaphragm fatigue in this setting. Prolonged controlled mechanical ventilation and diaphragm inactivity results in decreased diaphragm activation and contractility. Changes in neurophysiologic measures and diaphragm muscle fiber morphology indicate that the contractile dysfunction seen occurs at the level of diaphragm muscle rather than in nerve conduction or neuromuscular transmission

Influence of altitude on cerebral and splanchnic oxygen saturation in critically ill children during air ambulance transport.

ObjectiveThe aim of the current study was to investigate how cerebral and splanchnic oxygen saturation (rSO2-C and rSO2-A) in critically ill children transported in air ambulance was affected by flight with cabin pressurization corresponding to ≥ 5000 feet. A second aim was to investigate any differences between cyanotic and non-cyanotic children in relation to cerebral and splanchnic oxygen saturation during flight ≥ 5000 feet. The variability of the cerebral and splanchnic Near Infrared Spectroscopy (NIRS) sensors was evaluated.DesignNIRS was used to measure rSO2-C and rSO2-A during transport of critically ill children in air ambulance. rSO2 data was collected and stored by the NIRS monitor and extracted and analyzed off-line after the transport. Prior to evaluation of the NIRS signals all zero and floor-effect values were removed.SettingThe Pediatric Intensive Care Unit (PICU) at Astrid Lindgren Children's Hospital, Karolinska University Hospital in Stockholm, Sweden.PatientsIn total, 44 critically ill children scheduled for inter-hospital transport by a specialized pediatric transport team were included in the study between January 2014 and January 2019 (convenience sampling).InterventionNo interventions were conducted.MeasurementsAll study patients were monitored with a cerebral NIRS-sensor placed over the forehead and an abdominal NIRS-sensor placed in the infra-umbilical area for cerebral and splanchnic regional oxygen saturation monitoring, rSO2-C and rSO2-A, respectively.Main resultsComplete rSO2-C and rSO2-A data was obtained in 39 patients. Median age was 12 days. Cyanotic congenital heart malformations were present in 9 patients (23%). In 22 patients (56%) rSO2-C decreased at altitude ≥ 5000 feet and in 24 patients (61%) rSO2-A decreased at altitude ≥ 5000 feet compared to baseline (pConclusionBoth cerebral and splanchnic oxygen saturation decreased at altitude ≥ 5000 feet compared to baseline. In most patients, both cyanotic and non-cyanotic, cerebral oxygen saturation was preserved more than splanchnic oxygen saturation