Hypoxemia during procedural sedation in adult patients: a retrospective observational study.

PURPOSE: Since 2010, new guidelines for procedural sedation and the Helsinki Declaration on Patient Safety have increased patient safety, comfort, and acceptance considerably. Nevertheless, the administration of sedatives and opioids during sedation procedures may put the patient at risk of hypoxemia. However, data on hypoxemia during procedural sedation are scarce. Here, we studied the incidence and severity of hypoxemia during procedural sedations in our hospital. METHODS: A historical, single-centre cohort study was performed at the University Medical Centre Utrecht (UMCU), a tertiary centre in the Netherlands. Data from procedural sedation in our hospital between 1 January 2011 and 31 December 2018 (3,459 males and 2,534 females; total, 5,993) were extracted from our Anesthesia Information Management System. Hypoxemia was defined as peripheral oxygen saturation < 90% lasting at least two consecutive minutes. The severity of hypoxemia was calculated as area under the curve. The relationship between the severity of hypoxemia and body mass index (BMI), American Society of Anesthesiologists (ASA) Physical Status classification, and duration of the procedure was investigated. The primary outcome was the incidence of hypoxemia. RESULTS: Twenty-nine percent of moderately to deeply sedated patients developed hypoxemia. A high incidence of hypoxemia was found in patients undergoing procedures in the heart catheterization room (54%) and in patients undergoing bronchoscopy procedures (56%). Hypoxemia primarily occurred in longer lasting procedures (> 120 min) and especially in the latter phases of the procedures. There was no relationship between severity of hypoxemia and BMI or ASA Physical Status. CONCLUSIONS: This study showed that a considerable number of patients are at risk of hypoxemia during procedural sedation with a positive correlation shown with increasing duration of medical procedures. Additional prospective research is needed to investigate the clinical consequences of this cumulative hypoxemia.

RéSUMé: OBJECTIF: Depuis 2010, les nouvelles lignes directrices pour la sédation procédurale et la Déclaration d'Helsinki concernant la sécurité des patients ont considérablement augmenté la sécurité, le confort et l'acceptation des patients. L'administration de sédatifs et d'opioïdes pendant les interventions sous sédation peut toutefois mettre le patient à risque d'hypoxémie. Cependant, les données concernant l'hypoxémie pendant une sédation procédurale sont rares. Ici, nous avons étudié l'incidence et la sévérité de l'hypoxémie pendant la sédation procédurale dans notre hôpital. MéTHODE: Une étude de cohorte historique monocentrique a été réalisée au Centre médical universitaire d'Utrecht (UMCU), un centre tertiaire aux Pays-Bas. Les données des sédations procédurales réalisées dans notre hôpital entre le 1er janvier 2011 et le 31 décembre 2018 (3459 hommes et 2534 femmes; au total, 5993 patients) ont été extraites de notre système de gestion de l'information en anesthésie. L'hypoxémie a été définie comme une saturation périphérique en oxygène < 90 % durant au moins deux minutes consécutives. La sévérité de l'hypoxémie a été calculée en tant que surface sous la courbe. Les relations entre la sévérité de l'hypoxémie et l'indice de masse corporelle (IMC), la classification du statut physique selon l'American Society of Anesthesiologists (ASA) et la durée de l'intervention ont été étudiées. Le critère d'évaluation principal était l'incidence d'hypoxémie. RéSULTATS: Vingt-neuf pour cent des patients sous sédation modérée à profonde ont développé une hypoxémie. Une incidence élevée d'hypoxémie a été observée chez les patients subissant des interventions en salle d'hémodynamie (54 %) et chez les patients subissant des bronchoscopies (56 %). L'hypoxémie est principalement survenue lors d'interventions plus longues (> 120 min) et particulièrement dans les phases plus tardives des interventions. Aucune relation n'a été observée entre la sévérité de l'hypoxémie et l'IMC ou le statut physique ASA. CONCLUSION: Cette étude a démontré qu'un nombre considérable de patients sont à risque d'hypoxémie pendant la sédation procédurale, une corrélation positive ayant été démontrée avec une durée prolongée des interventions médicales. D'autres recherches prospectives sont nécessaires pour étudier les conséquences cliniques de cette hypoxémie cumulée.

Excessive Extracellular ATP Desensitizes P2Y2 and P2X4 ATP Receptors Provoking Surfactant Impairment Ending in Ventilation-Induced Lung Injury.

Stretching the alveolar epithelial type I (AT I) cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP) (purinergic signaling). Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases. When extracellular ATP reaches levels >100 μM, the ATP receptors of the AT II cells become desensitized and surfactant impairment is initiated. The resulting alteration in viscoelastic properties and in alveolar opening and collapse time-constants leads to alveolar collapse and the redistribution of inspired air from the alveoli to the alveolar ducts, which become pathologically dilated. The collapsed alveoli connected to these dilated alveolar ducts are subject to a massive strain, exacerbating the ATP release. After reaching concentrations >300 μM extracellular ATP acts as a danger-associated molecular pattern, causing capillary leakage, alveolar space edema, and further deactivation of surfactant by serum proteins. Decreasing the tidal volume to 6 mL/kg or less at this stage cannot prevent further lung injury.

Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury.

Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-ß, α-SMA, etc.) followed by the establishment of lung fibrosis.

Detection of 'best' positive end-expiratory pressure derived from electrical impedance tomography parameters during a decremental positive end-expiratory pressure trial.

INTRODUCTION: This study compares different parameters derived from electrical impedance tomography (EIT) data to define 'best' positive end-expiratory pressure (PEEP) during a decremental PEEP trial in mechanically-ventilated patients. 'Best' PEEP is regarded as minimal lung collapse and overdistention in order to prevent ventilator-induced lung injury. METHODS: A decremental PEEP trial (from 15 to 0 cm H2O PEEP in 4 steps) was performed in 12 post-cardiac surgery patients on the ICU. At each PEEP step, EIT measurements were performed and from this data the following were calculated: tidal impedance variation (TIV), regional compliance, ventilation surface area (VSA), center of ventilation (COV), regional ventilation delay (RVD index), global inhomogeneity (GI index), and intratidal gas distribution. From the latter parameter we developed the ITV index as a new homogeneity parameter. The EIT parameters were compared with dynamic compliance and the PaO2/FiO2 ratio. RESULTS: Dynamic compliance and the PaO2/FiO2 ratio had the highest value at 10 and 15 cm H2O PEEP, respectively. TIV, regional compliance and VSA had a maximum value at 5 cm H2O PEEP for the non-dependent lung region and a maximal value at 15 cm H2O PEEP for the dependent lung region. GI index showed the lowest value at 10 cm H2O PEEP, whereas for COV and the RVD index this was at 15 cm H2O PEEP. The intratidal gas distribution showed an equal contribution of both lung regions at a specific PEEP level in each patient. CONCLUSION: In post-cardiac surgery patients, the ITV index was comparable with dynamic compliance to indicate 'best' PEEP. The ITV index can visualize the PEEP level at which ventilation of the non-dependent region is diminished, indicating overdistention. Additional studies should test whether application of this specific PEEP level leads to better outcome and also confirm these results in patients with acute respiratory distress syndrome.

Ventilation distribution measured with EIT at varying levels of pressure support and Neurally Adjusted Ventilatory Assist in patients with ALI.

PURPOSE: The purpose of this study was to compare the effect of varying levels of assist during pressure support (PSV) and Neurally Adjusted Ventilatory Assist (NAVA) on the aeration of the dependent and non-dependent lung regions by means of Electrical Impedance Tomography (EIT). METHODS: We studied ten mechanically ventilated patients with Acute Lung Injury (ALI). Positive-End Expiratory Pressure (PEEP) and PSV levels were both 10 cm H2O during the initial PSV step. Thereafter, we changed the inspiratory pressure to 15 and 5 cm H2O during PSV. The electrical activity of the diaphragm (EAdi) during pressure support ten was used to define the initial NAVA gain (100 %). Thereafter, we changed NAVA gain to 150 and 50 %, respectively. After each step the assist level was switched back to PSV 10 cm H2O or NAVA 100 % to get a new baseline. The EIT registration was performed continuously. RESULTS: Tidal impedance variation significantly decreased during descending PSV levels within patients, whereas not during NAVA. The dorsal-to-ventral impedance distribution, expressed according to the center of gravity index, was lower during PSV compared to NAVA. Ventilation contribution of the dependent lung region was equally in balance with the non-dependent lung region during PSV 5 cm H2O, NAVA 50 and 100 %. CONCLUSION: Neurally Adjusted Ventilatory Assist ventilation had a beneficial effect on the ventilation of the dependent lung region and showed less over-assistance compared to PSV in patients with ALI.

Lung monitoring at the bedside in mechanically ventilated patients.

PURPOSE OF REVIEW: It has become clear that mechanical ventilation itself can cause damage to the lung in critically ill patients, also known as ventilator-induced lung injury (VILI). Insight into the mechanisms of VILI has learned that a compromise must be found between positive end-expiratory pressure (PEEP) induced alveolar recruitment and prevention of hyperinflation. Therefore, there is a need for clinicians to optimize the PEEP settings for the individual patient at the bedside. In this review, we will discuss several lung-monitoring techniques to improve patient ventilator settings. RECENT FINDINGS: Recently, new monitoring tools like electrical impedance tomography (EIT), vibration response imaging, respiratory inductive plethysmography and functional residual capacity (FRC) have been (re-)introduced in our ICU. Nowadays, FRC can be measured without the use of tracer gases and without disconnection from the ventilator. EIT is another noninvasive bedside monitoring tool that provides regional ventilation distribution images and can be used for qualitative and quantitative assessment of regional change in ventilation after a ventilator change. These new noninvasive techniques are discussed and seem promising to help clinicians to improve their ventilator settings in the individual patient at the bedside. SUMMARY: In conclusion, both FRC and EIT are promising clinical monitoring systems but clinical studies are needed to prove whether these monitors help the clinician toward effective and better ventilator management.