Investigating the Effect of Expiratory Time Constant on Outcome in Intubated Patients with Acute Respiratory Failure Caused by COVID-19 in Critical Care Unit: A Research Study

Background: The coronavirus disease 2019 (COVID-19) has a high prevalence and mortality worldwide. Thousands of patients with acute respiratory failure caused by COVID-19 are daily hospitalized in intensive care units (ICUs) around the world. Many of these patients require full mechanical respiratory support and long-term ventilator use. Using different ventilators and calculating important variables can be helpful in meeting therapeutic needs of patients. Objectives: The aim of present study was to investigate the effect of expiratory time constant (RCEXP) on the course of treatment and duration of mechanical ventilation in patients with acute respiratory failure hospitalized in ICU. Methods: The present cross-sectional study was conducted on 60 patients with acute respiratory failure who were hospitalized in the ICU and underwent mechanical ventilation due to COVID-19 in the first six months of 2020. The variables of RCEXP, lung compliance and lung resistance in all patients were recorded daily and analyzed. Then, based on clinical outcome, the patients were divided into two groups: the patients with wean outcome (N = 40) and those with death outcome (N = 20). Results: The mean ± SD of lung compliance in patients who were separated from ventilator and patients with death outcome were 74.73 (18.58) mL/cm H2O and 36.92 (10.56) mL/cm H2O, respectively, which was statistically significant (P = 0.001). The mean ± SD of lung resistance in patients who were separated from ventilator and patients with death outcome were calculated at 9.25 (4.62) and 14 (6.5), respectively, which was statistically significant (P = 0.015). Also, there was a statistically significant difference between the two groups in terms of mean ± SD of RCEXP (0.67 (0.23) vs. 0.49 (0.19), P = 0.010). Conclusions: According to the results of this study, there was a significant difference between high resistance, low compliance, RCEXP, and weaning success of intubation in patients hospitalized in the ICU.

End-Tidal Carbon Dioxide Pressure Measurement after Prolonged Inspiratory Time Gives a Good Estimation of the Arterial Carbon Dioxide Pressure in Mechanically Ventilated Patients

Background: End-tidal carbon dioxide pressure (PetCO2) is unreliable for monitoring PaCO2 in several conditions because of the unpredictable value of the PaCO2–PetCO2 gradient. We hypothesised that increasing both the end-inspiratory pause and the expiratory time would reduce this gradient in patients ventilated for COVID-19 with Acute Respiratory Distress Syndrome and in patients anaesthetised for surgery. Methods: On the occasion of an arterial blood gas sample, an extension in inspiratory pause was carried out either by recruitment manoeuvre or by extending the end-inspiratory pause to 10 s. The end-expired PCO2 was measured (expiratory time: 4 s) after this manoeuvre (PACO2) in comparison with the PetCO2 measured by the monitor. We analysed 67 Δ(a-et)CO2, Δ(a-A)CO2 pairs for 7 patients in the COVID group and for 27 patients in the anaesthesia group. Results are expressed as mean ± standard deviation. Results: Prolongation of the inspiratory pause significantly reduced PaCO2–PetCO2 gradients from 11 ± 5.7 and 5.7 ± 3.4 mm Hg (p < 0.001) to PaCO2–PACO2 gradients of −1.2 ± 3.3 (p = 0.043) and −1.9 ± 3.3 mm Hg (p < 0.003) in the COVID and anaesthesia groups, respectively. In the COVID group, PACO2 showed the lowest dispersion (−7 to +6 mm Hg) and better correlation with PaCO2 (R2 = 0.92). The PACO2 had a sensitivity of 0.81 and a specificity of 0.93 for identifying hypercapnic patients (PaCO2 > 50 mm Hg). Conclusions: Measuring end-tidal PCO2 after prolonged inspiratory time reduced the PaCO2–PetCO2 gradient to the point of obtaining values close to PaCO2. This measure identified hypercapnic patients in both intensive care and during anaesthesia.

Volatile anesthetics maintain tidal volume and minute ventilation to a greater degree than propofol under spontaneous respiration

Background Although general anesthetics depress spontaneous respiration, the comprehensive effect of general anesthetics on respiratory function remains unclear. We aimed to investigate the effects of general anesthetics on spontaneous respiration in non-intubated mice with different types and doses of general anesthetic. Methods Adult C57BL/6 J mice were administered intravenous anesthetics, including propofol and etomidate, and inhalational anesthetics, including sevoflurane and isoflurane in vivo at doses of 0.5-, 1.0-, and 2.0-times the minimum alveolar concentration (MAC)/median effective dose (ED50) to induce loss of the righting reflex (LORR). Whole-body plethysmography (WBP) was applied to measure parameters of respiration under unrestricted conditions without endotracheal intubation. The alteration in respiratory sensitivity to carbon dioxide (CO2) under general anesthesia was also determined. The following respiratory parameters were continuously recorded during anesthesia or CO2 exposure: respiratory frequency (FR), tidal volume (TV), minute ventilation (MV), expiratory time (TE), inspiratory time (TI), and inspiratory–expiratory time ratio (I/E), and peak inspiratory flow. Results Sub-anesthetic concentrations (0.5 MAC) of sevoflurane or isoflurane increased FR, TV, and MV. With isoflurane and sevoflurane exposure, the CO2-evoked increases in FR, TV, and MV were decreased. Compared with inhalational anesthetics, propofol and etomidate induced respiratory suppression, affecting FR, TV, and MV. In 100% oxygen (O2), FR in the group that received propofol 1.0-times the ED50 was 69.63 ± 33.44 breaths/min compared with 155.68 ± 64.42 breaths/min in the etomidate-treated group. In the same groups, FR was 88.72 ± 34.51 breaths/min and 225.10 ± 59.82 breaths/min, respectively, in 3% CO2 and 144.17 ± 63.25 breaths/min and 197.70 ± 41.93 breaths/min, respectively, in 5% CO2. A higher CO2 sensitivity was found in etomidate-treated mice compared with propofol-treated mice. In addition, propofol induced a greater decrease in FR, MV, and I/E ratio compared with etomidate, sevoflurane, and isoflurane at equivalent doses (all P < 0.05). Conclusions General anesthetics differentially modulate spontaneous breathing in vivo. Volatile anesthetics increase FR, TV, and MV at sub-anesthetic concentrations, while they decrease FR at higher concentrations. Propofol consistently depressed respiratory parameters to a greater degree than etomidate.

Coordination of Respiration, Swallowing, and Chewing in Healthy Young Adults

Examining the coordination of respiration and swallowing is important for elucidating the mechanisms underlying these functions and assessing how respiration is linked to swallowing impairment in dysphagic patients. In this study, we assessed the coordination of respiration and swallowing to clarify how voluntary swallowing is coordinated with respiration and how mastication modulates the coordination of respiration and swallowing in healthy humans. Twenty-one healthy volunteers participated in three experiments. The participants were asked to swallow 3 ml of water with or without a cue, to drink 100 ml of water using a cup without breathing between swallows, and to eat a 4-g portion of corned beef. The major coordination pattern of respiration and swallowing was expiration–swallow–expiration (EE type) while swallowing 3 ml of water either with or without a cue, swallowing 100 ml of water, and chewing. Although cueing did not affect swallowing movements, the expiratory time was lengthened with the cue. During 100-ml water swallowing, the respiratory cycle time and expiratory time immediately before swallowing were significantly shorter compared with during and after swallowing, whereas the inspiratory time did not differ throughout the recording period. During chewing, the respiratory cycle time was decreased in a time-dependent manner, probably because of metabolic demand. The coordination of the two functions is maintained not only in voluntary swallowing but also in involuntary swallowing during chewing. Understanding the mechanisms underlying respiration and swallowing is important for evaluating how coordination affects physiological swallowing in dysphagic patients.

Neonatal Resuscitation With T-Piece Systems: Risk of Inadvertent PEEP Related to Mechanical Properties

Background: Resuscitation of infants using T-piece resuscitators (TPR) allow positive pressure ventilation with positive end-expiratory pressure (PEEP). The adjustable PEEP valve adds resistance to expiration and could contribute to inadvertent PEEP. The study indirectly investigated risk of inadvertent peep by determining expiratory time constants. The aim was to measure system expiratory time constants for a TPR device in a passive mechanical model with infant lung properties.Methods: We used adiabatic bottles to generate four levels of compliance (0.5–3.4 mL/cm H2O). Expiratory time constants were recorded for combinations of fresh gas flow (8, 10, 15 L/min), PEEP (5, 8, 10 cm H2O), airway resistance (50, 200 cm H2O/L/sec and none), endotracheal tube (none, size 2.5, 3.0, 3.5) with a peak inflation pressure of 15 cm H2O above PEEP.Results: Low compliances resulted in time constants below 0.17 s contrasting to higher compliances where the expiratory time constants were 0.25–0.81 s. Time constants increased with increased resistance, lower fresh gas flows, higher set PEEP levels and with an added airway resistance or endotracheal tube.Conclusions: The risk of inadvertent PEEP increases with a shorter time for expiration in combination with a higher compliance or resistance. The TPR resistance can be reduced by increasing the fresh gas flow or reducing PEEP. The expiratory time constants indicate that this may be clinically important. The risk of inadvertent PEEP would be highest in intubated term infants with highly compliant lungs. These results are useful for interpreting clinical events and recordings.

Diaphragm Ultrasography to Predict Respiratory Failure in Infants with Severe Bronchiolitis

Objetive: To evaluate the ultrasonographic contractile activity indices of the diaphragm in infants with moderate and severe bronchiolitis supported with high-flow nasal cannula (HFNC) or non-invasive ventilation (NIV) to predict the need of invasive mechanical ventilation (IMV). Methods: Prospective observational study in infants admitted to a Pediatric Intensive Care Unit (PICU). Diaphragmatic excursion (dEx), diaphragmatic inspiratory (dTi) and expiratory time (dTe), and fraction of diaphragmatic thickening (dTF) were recorded at admission, 24 h and 48 h in both diaphragms. RESULTS: Twenty-six patiens were included (14 on HFNC and 12 on NIV) with a total of 56 ultrasonographic evaluations. Three patients required IMV. Sixty-four percent of the patients on HFNC required NIV as rescue therapy and 2/14 IMV (14,2%). In the HFNC group there were no differences in dEx between those who required escalation to NIV or IMV and those who didn’t. Diaphragmatic left thickening fraction (Left dTF) increased in patients on HFNC requiring IMV vs those needing NIV (Left dTF 47% vs 22% (13-30); p=0,046, r=0,7) (Fig 2). Diaphragmatic inspiratory time was higher in infants on HFNC requiring IMV and diaphragmatic expiratory time was shorter (dLET, p=0,038; dRET, p=0,022). In the NIV group there were no diffenreces in dEx, dTi, dTe or dTF between patients needing escalation to IMV and those who didn’t. We found no correlation between a clinical score and echographic dTF. CONCLUSION: In infants with moderate or severe brochiolitis receiving HFNC the use of ultrasonographic left dTF could help predict respiratory failure (RF) and need for IMV. The use of ultrasonographic diaphragmatic excursion is of little help to predict both.

Forced Expiratory Time: A Composite of Airway Narrowing and Airway Closure

Forced expiratory time (FET) is a spirometrically-derived variable thought to reflect lung function, but its physiologic basis remains poorly understood. We developed a mathematical theory of FET assuming a linear forced expiratory flow-volume profile that terminates when expiratory flow falls below a defined detection threshold. FET is predicted to correlate negatively with both FEV1 and FVC if variations in the rate of lung emptying (relative to normal) among individuals in a population exceed variations in the amount of lung emptying. We retrospectively determined FET pre- and post-methacholine challenge in 1241 patients (818 had normal lung function, 137 were obstructed, and 229 were restricted) and examined its relationships to spirometric and demographic variables in both hyperresponsive and normoresponsive individuals. Mean FET was 9.6 ± 2.2 s in the normal group, 12.3 ± 3.0 s in those with obstruction, and 8.8 ± 1.9 s in those with restriction. FET was inversely related to FEV1/FVC in all groups, negatively related to FEV1 in the obstructed patients, and positively related to FVC in both the normal and restricted patients. There was no relationship with methacholine responsiveness. Overall, our theory of the relationship between FET to the spirometric indices is supported by these findings, and in addition potentially explains how FET is affected by gender, age, smoking status, and possibly body mass index.

Miniature Transport Respirator Performance Evaluation for Ventilatory Support

In the face of the coronavirus pandemic (COVID-19), in hospital and emergency units, there is low availability of mechanical respirator for patients in need of this support, greatly improving the survival rate. In these situations, there is a need for simpler equipment, easy access, low cost, and fast manufacturing. In this study, a 3D prototype transport respirator was developed using as a model the Takaoka 600 Mini Respirator, national technology from the 1950s. The influence of adjustable parameters of the respirator was evaluated to understand it is functioning: maximum and minimum lung pressure; respirator intake pressure; respiratory rate; inspiratory and expiratory time according to the sensitivity of the mini respirator; and pressure and flow of O₂ line intake. The increase in sensitivity led to an increase in maximum and minimum pulmonary pressure, decreased inspiratory and expiratory time, with margins of 1/1, 1/2, 1/3 inspiratory/expiratory time ratio (I/E ratio). The intake flow of O₂ varied proportionally with the pressure of air intake into the respirator, with its increase leading to an increase in respiratory rate, without major influences on lung pressure and the I/E ratio. The O₂ line intake pressure without major influences on lung pressure, showing and I/E ratio >1 in values below 3.5 kPa x 100. In conclusion, it was possible to obtain a pulmonary ventilator-dependent only on positive O₂ flow, compact and effective for patient transport, and in cases of emergencies with control of maximum pressure and respiratory rate offered to the patient. Among the parameters evaluated for this respirator, an line pressure of O₂ from 3.5 kPa x 100, sensitivity between 3 and 5, a flow of 5 to 15 L/min is recommended.