Adolescent Congenital Central Hypoventilation Syndrome: An Easily Overlooked Diagnosis

Congenital central hypoventilation syndrome (CCHS), also known as Ondine’s curse, is a rare, potentially fatal genetic disease, manifesting as a lack of respiratory drive. Most diagnoses are made in pediatric patients, however late-onset cases have been rarely reported. Due to the milder symptoms at presentation that might easily go overlooked, these late-onset cases can result in serious health consequences later in life. Here, we present a case report of late-onset CCHS in an adolescent female patient. In this review we summarize the current knowledge about symptoms, as well as clinical management of CCHS, and describe in detail the molecular mechanism responsible for this disorder.

Proportional assist ventilation relieves clinically significant dyspnea in critically ill ventilated patients

Introduction Dyspnea is common and often severe symptom in mechanically ventilated patients. Proportional assist ventilation (PAV) is an assist ventilatory mode that adjusts the level of assistance to the activity of respiratory muscles. We hypothesized that PAV reduce dyspnea compared to pressure support ventilation (PSV). Patients and methods Mechanically ventilated patients with clinically significant dyspnea were included. Dyspnea intensity was assessed by the Dyspnea—Visual Analog Scale (D-VAS) and the Intensive Care-Respiratory Distress Observation Scale (IC-RDOS) at inclusion (PSV-Baseline), after personalization of ventilator settings in order to minimize dyspnea (PSV-Personalization), and after switch to PAV. Respiratory drive was assessed by record of electromyographic activity of inspiratory muscles, the proportion of asynchrony was analyzed. Results Thirty-four patients were included (73% males, median age of 66 [57–77] years). The D-VAS score was lower with PSV-Personalization (37 mm [20‒55]) and PAV (31 mm [14‒45]) than with PSV-Baseline (62 mm [28‒76]) (p < 0.05). The IC-RDOS score was lower with PAV (4.2 [2.4‒4.7]) and PSV-Personalization (4.4 [2.4‒4.9]) than with PSV-Baseline (4.8 [4.1‒6.5]) (p < 0.05). The electromyographic activity of parasternal intercostal muscles was lower with PAV and PSV-Personalization than with PSV-Baseline. The asynchrony index was lower with PAV (0% [0‒0.55]) than with PSV-Baseline and PSV-Personalization (0.68% [0‒2.28] and 0.60% [0.31‒1.41], respectively) (p < 0.05). Conclusion In mechanically ventilated patients exhibiting clinically significant dyspnea with PSV, personalization of PSV settings and PAV results in not different decreased dyspnea and activity of muscles to a similar degree, even though PAV was able to reduce asynchrony more effectively.

Automatic Adjustment of the Inspiratory Trigger and Cycling-Off Criteria Improved Patient-Ventilator Asynchrony During Pressure Support Ventilation

Background: Patient-ventilator asynchrony is common during pressure support ventilation (PSV) because of the constant cycling-off criteria and variation of respiratory system mechanical properties in individual patients. Automatic adjustment of inspiratory triggers and cycling-off criteria based on waveforms might be a useful tool to improve patient-ventilator asynchrony during PSV.Method: Twenty-four patients were enrolled and were ventilated using PSV with different cycling-off criteria of 10% (PS10), 30% (PS30), 50% (PS50), and automatic adjustment PSV (PSAUTO). Patient-ventilator interactions were measured.Results: The total asynchrony index (AI) and NeuroSync index were consistently lower in PSAUTO when compared with PS10, PS30, and PS50, (P &lt; 0.05). The benefit of PSAUTO in reducing the total AI was mainly because of the reduction of the micro-AI but not the macro-AI. PSAUTO significantly improved the relative cycling-off error when compared with prefixed controlled PSV (P &lt; 0.05). PSAUTO significantly reduced the trigger error and inspiratory effort for the trigger when compared with a prefixed trigger. However, total inspiratory effort, breathing patterns, and respiratory drive were not different among modes.Conclusions: When compared with fixed cycling-off criteria, an automatic adjustment system improved patient-ventilator asynchrony without changes in breathing patterns during PSV. The automatic adjustment system could be a useful tool to titrate more personalized mechanical ventilation.

Effectiveness and safety of intravenous dexmedetomidine sedation for ophthalmic surgery under regional anesthesia

Purpose To assess the effectiveness and safety of intravenous (IV) dexmedetomidine for sedation in ophthalmic surgery. Methods Prospective, observational, uncontrolled, single-center study. Patients were sedated with a continuous dexmedetomidine IV infusion started 15 min before regional anesthesia administration and maintained up to the end of surgery. Effectiveness of dexmedetomidine was assessed by the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) targeted at 5. Safety was assessed by the incidence of patients’ movements/snoring and by the incidence of respiratory and haemodynamic complications. An eleven-point numerical rating scale (NRS) was used to assess the level of satisfaction of both the surgeon and the patient. Results 123 patients (73 males, mean age: 63 ± 13) were included; 81 (81/123; 65.8%) patients reached the requested MOAA/S score of 5. Any intraoperative movement – mostly voluntary – occurred in 34 (34/123; 27.6%) cases with no need for a switch to general anaesthesia; no ocular complications related to the intraoperative movements occurred. Intraoperative snoring occurred in 30 (30/123; 24.4%) patients and it did not affect the surgical manoeuvres. Respiratory drive depression requiring manual or mechanical ventilation never occurred. Bradycardia occurred in 14 (14/123; 11.3%), cases but only 4 (4/123; 3.2%) patients required atropine administration, which was always effective. Intraoperative analgesia was consistently obtained and both the surgeons and the patients reported a high NRS satisfaction score. Conclusion Dexmedetomidine provided adequate sedation in patients undergoing ocular surgery under local anaesthesia and showed a good effectiveness and safety profile. Upper airway obstruction, apnoea and snoring can occur.

Clinical Sleep-Related Breathing Disorders

Sleep-related breathing disorders are categorized into obstructive sleep apnea syndromes, central sleep apnea syndrome, and sleep-related hypoventilation or hypoxic syndromes. These disorders can occur in adults and children. Clinical characteristics, diagnosis, and treatment are discussed in this chapter. Sleep apnea occurs when recurrent complete (apnea) or nearly complete (hypopnea) cessation of airflow develops, accompanied by preservation of the respiratory drive manifested as persistent respiratory muscle effort. Apnea is defined as the cessation of airflow for more than 10 seconds, using a valid measure of airflow. Hypopnea is an airflow reduction of at least 30% from baseline that lasts at least 10 seconds and is accompanied by an oxygen desaturation of 4% or more.

COVID-19 pneumonia: pathophysiology and management

Coronavirus disease 2019 (COVID-19) pneumonia is an evolving disease. We will focus on the development of its pathophysiologic characteristics over time, and how these time-related changes determine modifications in treatment. In the emergency department: the peculiar characteristic is the coexistence, in a significant fraction of patients, of severe hypoxaemia, near-normal lung computed tomography imaging, lung gas volume and respiratory mechanics. Despite high respiratory drive, dyspnoea and respiratory rate are often normal. The underlying mechanism is primarily altered lung perfusion. The anatomical prerequisites for PEEP (positive end-expiratory pressure) to work (lung oedema, atelectasis, and therefore recruitability) are lacking. In the high-dependency unit: the disease starts to worsen either because of its natural evolution or additional patient self-inflicted lung injury (P-SILI). Oedema and atelectasis may develop, increasing recruitability. Noninvasive supports are indicated if they result in a reversal of hypoxaemia and a decreased inspiratory effort. Otherwise, mechanical ventilation should be considered to avert P-SILI. In the intensive care unit: the primary characteristic of the advance of unresolved COVID-19 disease is a progressive shift from oedema or atelectasis to less reversible structural lung alterations to lung fibrosis. These later characteristics are associated with notable impairment of respiratory mechanics, increased arterial carbon dioxide tension (PaCO2), decreased recruitability and lack of response to PEEP and prone positioning.

Respiratory Drive in Patients with Sepsis and Septic Shock: Modulation by High-flow Nasal Cannula

Background Experimental and pilot clinical data suggest that spontaneously breathing patients with sepsis and septic shock may present increased respiratory drive and effort, even in the absence of pulmonary infection. The study hypothesis was that respiratory drive and effort may be increased in septic patients and correlated with extrapulmonary determinant and that high-flow nasal cannula may modulate drive and effort. Methods Twenty-five nonintubated patients with extrapulmonary sepsis or septic shock were enrolled. Each patient underwent three consecutive steps: low-flow oxygen at baseline, high-flow nasal cannula, and then low-flow oxygen again. Arterial blood gases, esophageal pressure, and electrical impedance tomography data were recorded toward the end of each step. Respiratory effort was measured as the negative swing of esophageal pressure (ΔPes); drive was quantified as the change in esophageal pressure during the first 500 ms from start of inspiration (P0.5). Dynamic lung compliance was calculated as the tidal volume measured by electrical impedance tomography, divided by ΔPes. The results are presented as medians [25th to 75th percentile]. Results Thirteen patients (52%) were in septic shock. The Sequential Organ Failure Assessment score was 5 [4 to 9]. During low-flow oxygen at baseline, respiratory drive and effort were elevated and significantly correlated with arterial lactate (r = 0.46, P = 0.034) and inversely with dynamic lung compliance (r = –0.735, P &lt; 0.001). Noninvasive support by high-flow nasal cannula induced a significant decrease of respiratory drive (P0.5: 6.0 [4.4 to 9.0] vs. 4.3 [3.5 to 6.6] vs. 6.6 [4.9 to 10.7] cm H2O, P &lt; 0.001) and effort (ΔPes: 8.0 [6.0 to 11.5] vs. 5.5 [4.5 to 8.0] vs. 7.5 [6.0 to 12.6] cm H2O, P &lt; 0.001). Oxygenation and arterial carbon dioxide levels remained stable during all study phases. Conclusions Patients with sepsis and septic shock of extrapulmonary origin present elevated respiratory drive and effort, which can be effectively reduced by high-flow nasal cannula. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

14 Diaphragmatic Electrical Activity in Preterm Infants on Non-Invasive High Frequency Oscillatory Ventilation (DEAP-NHFO Study)

Primary Subject area Neonatal-Perinatal Medicine Background Continuous Positive Airway Pressure (CPAP) is a common form of non-invasive respiratory support for preterm infants. Non-invasive high frequency ventilation (NHFOV) is a relatively new method of non-invasive respiratory support. NHFOV is being increasingly utilized in clinical practice in an attempt to prevent intubation and minimize ventilator-induced lung injury in preterm infants. Preliminary studies suggest superiority of NHFOV over CPAP, but little is known about its mechanism of action and its effect on respiratory control in the newborn. We hypothesize that NHFOV reduces respiratory drive and improves ventilation, resulting in decreased patient diaphragm energy expenditure, which can be assessed by measuring the electrical activity of the diaphragm (Edi). Objectives The objective of this study is to compare the effects of non-invasive respiratory support delivered by nasal CPAP versus NHFOV on respiratory pattern, as assessed by the Edi in very low birth weight (VLBW) preterm infants. Design/Methods In a prospective, randomized, crossover study, 20 preterm infants with birth weights ≤1500 g requiring CPAP were randomized to either NHFOV or CPAP for 105 min, followed by crossover to the other method for the same duration. Edi was continuously measured by a feeding catheter with miniaturized sensors embedded in its wall (Maquet, Solna). The general sequence was 15 minutes for acclimation to the mode, 75 minutes for a feed to be completed, followed by 15 minutes for breath-by-breath analyses of neural breathing pattern. Primary outcome was difference in the peak Edi between CPAP and NHFOV. Secondary outcomes included difference in other measures of respiratory drive: neural respiratory rate, neural inspiratory time, diaphragm energy expenditure, transcutaneous pCO2, number of apnea episodes on the Edi, and episodes of clinically significant apnea. Results No significant differences in Edi timing, Edi min, Edi peak, apnea, or CO2 were observed between the two modes of respiratory support. Conclusion In this cohort of VLBW preterm infants, neural respiratory pattern was not significantly different between NHFOV and CPAP. With this baseline information in stable preterm infants, it would now be important to assess whether these results hold true in infants with more severe lung disease, where NHFOV is often used as escalating support from CPAP.

Epidural morphine in COVID ARDS patients with high respiratory drive: a structured summary of a study protocol for a randomised controlled trial

Objectives We aim to study the effect of epidural morphine as a means to reduce high respiratory drive in COVID 19 patients on non-invasive ventilation (NIV)—primary end point—and to study its effect on respiratory parameters, subjective patient comfort, rates of endotracheal intubation, duration of mechanical ventilation and mortality. Trial design Parallel group, randomised, double blind, single centre placebo control trial. Allocation ratio 1:1, superiority trial Participants Trial site and population—COVID ICU patients in the All India Institute of Medical Sciences (AIIMS) Bhubaneswar, Odisha, India Inclusion and exclusion criteria Inclusion criteria Adult patients on NIV with COVID-19 Exclusion criteria Metabolic acidosis HCO3-< 16 and pH < 7.2. Severe hypoxemia warranting cessation of NIV and intubation, non-acceptance of NIV and proven sepsis. Technical difficulty for epidural catheterization, coagulation abnormalities, low respiratory drive and EOL orders. Sources or methods of recruitment—daily discussion at 8 am of new admissions to COVID ICU on NIV—consenting adult patients with COVID19 on NIV and high respiratory drive; not meeting exclusion criteria will be recruited for the trial and randomised. Intervention and comparator Patients of both groups will be turned to a lateral or sitting position (as comfortable), and an injection of local anaesthetic be given at lumbar 2–3/3–4 space. In the intervention group, an epidural catheter will be inserted using aseptic technique and fixed to the skin. The control group will have a sham catheter fixed exactly like in the intervention group, but not entering the epidural space. The intervention group will be administered injection morphine sulphate once every 18–24 h into the epidural space. The doses will be escalated daily (5–10 mg), titrated to effect: escalation limited by hypoventilation resulting in respiratory acidosis (pH < 7.2). The intervention will continue for a minimum of 2 doses and a maximum of 5 doses (96 h) of morphine. It will be stopped if the epidural catheter gets dislodged before the second dose or the patient is weaned off non-invasive ventilation to high flow mask for a continuous period of 24 h or requires endotracheal intubation. The patient will be followed up till death or 28 days after ICU discharge. Main outcomes Primary outcome—diaphragm thickening index fraction (average of minimum 3 readings) Secondary outcomes—ventilator parameters, sedation and pain scores, subjective comfort and dyspnoea scores, time to intubation, length of stay on NIV and 28-day mortality Timing of outcome assessment—every 8th hour assessment for 24 h after the last dose of epidural morphine or 120 h whichever is greater Randomisation A central random number list will be kept with the study research assistant. She will randomise according to the numbers available in the list using an allocation ratio of 1:1. An opaque sealed envelope concealing the allotted randomisation code will be dispatched to the ICU team. Blinding (masking) The assessor, patient, nurses and physicians will be blind to group allocation. One member of the team not involved in research will administer the intervention. Numbers to be randomised (sample size) Twenty-five patients per group; 50 patients total Trial status Protocol version 1. Not recruiting yet. Recruitment to begin by 24 July 2021 and end by 31 August 2022 Trial registration Central Trials Registry India CTRI CTRI/2021/07/035093. Registered on 23 July 2021. Prospectively registered Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

Air leak syndrome in COVID-19 – A case series

Air leak syndrome manifesting as pneumomediastinum (PM), pneumothorax (PNX) or subcutaneous emphysema (SCE) has been reported in COVID-19 patients with increasing frequency and with varying outcomes. We report a series of eight cases of PM or SCE from 1 April to May 31, 2021, among COVID-19 patients admitted in our ICU. All the patients had severe hypoxemia (PaO2/FiO2 ratio ≤100) and were on noninvasive ventilation when the air leak was detected except one. PM/SCE was observed mostly on the 3 to 5 day after instituting positive pressure ventilation. High respiratory drive with mean tidal volumes in the range of 6 to 10ml/kg predicted body weight was observed in these patients. Mean inspiratory pressure (Pressure support + positive end expiratory pressure) and mean positive end expiratory pressure delivered by the ventilator ranged between 11 to 21 and 5 to 12 cm HO respectively. Outcomes varied with four deaths, four patients requiring intubation, two patients requiring chest drainage and four patients showing overall improvement out of the total eight patients with air leak.1.Air leak syndrome is not rare in COVID-19 with reported incidence of 10-14%; 2. Spontaneous noninvasive ventilation in patients with high respiratory drive and large fluctuations in tidal volumes seems to be a risk factor for air leak in patients with severe lung involvement; 3. A conservative approach without intercostal drainage seems to be acceptable in the absence of pneumothorax; 4. Prognosis is varied depending on the underlying disease and not always catastrophic.