Early experience with critically ill patients with COVID-19 in Montreal.

PURPOSE: Montreal has been the epicentre of the coronavirus disease (COVID-19) pandemic in Canada. Given the regional disparities in incidence and mortality in the general population, we aimed to describe local characteristics, treatments, and outcomes of critically ill COVID-19 patients in Montreal. METHODS: A single-centre retrospective cohort of consecutive adult patients admitted to the intensive care unit (ICU) of Hôpital du Sacré-Coeur de Montréal with confirmed COVID-19 were included. RESULTS: Between 20 March and 13 May 2020, 75 patients were admitted, with a median [interquartile range (IQR)] age of 62 [53-72] yr and high rates of obesity (47%), hypertension (67%), and diabetes (37%). Healthcare-related infections were responsible for 35% of cases. The median [IQR] day 1 sequential organ failure assessment score was 6 [3-7]. Invasive mechanical ventilation (IMV) was used in 57% of patients for a median [IQR] of 11 [5-22] days. Patients receiving IMV were characterized by a moderately decreased median [IQR] partial pressure of oxygen:fraction of inspired oxygen (day 1 PaO2:FiO2 = 177 [138-276]; day 10 = 173 [147-227]) and compliance (day 1 = 48 [38-58] mL/cmH2O; day 10 = 34 [28-42] mL/cmH2O) and very elevated estimated dead space fraction (day 1 = 0.60 [0.53-0.67]; day 10 = 0.72 [0.69-0.79]). Overall hospital mortality was 25%, and 21% in the IMV patients. Mortality was 82% in patients ≥ 80 yr old. CONCLUSIONS: Characteristics and outcomes of critically ill patients with COVID-19 in Montreal were similar to those reported in the existing literature. We found an increased physiologic dead space, supporting the hypothesis that pulmonary vascular injury may be central to COVID-19-induced lung damage.

RéSUMé: OBJECTIF: Montréal a été l'épicentre de la pandémie du coronavirus (COVID-19) au Canada. Étant donné les disparités régionales dans l'incidence et la mortalité dans la population générale, nous avons tenté de décrire les caractéristiques locales, les traitements et le devenir des patients atteints de la COVID-19 en état critique à Montréal. MéTHODE: Notre étude de cohorte rétrospective monocentrique a inclus tous les patients adultes admis consécutivement à l'unité de soins intensifs de l'Hôpital du Sacré-Cœur de Montréal avec un diagnostic confirmé de COVID-19. RéSULTATS: Soixante-quinze patients ont été admis entre le 20 mars et le 13 mai 2020. Ceux-ci avaient un âge médian [écart interquartile (ÉIQ)] de 62 [53­72] ans et présentaient une incidence élevée d'obésité (47 %), d'hypertension (67 %) et de diabète (37 %). Les transmissions associées aux soins de santé étaient responsables de 35 % des cas. Au jour 1, le score SOFA (Sequential Organ Failure Assessment ­ évaluation séquentielle de défaillance des organes) médian [ÉIQ] était de 6 [3­7]. La ventilation mécanique invasive (VMI) a été utilisée chez 57 % des patients, pour une durée médiane [ÉIQ] de 11 [5­22] jours. Les patients ayant reçu une VMI étaient caractérisés par une médiane [ÉIQ] modérément réduite de la pression partielle de la fraction d'oxygène inspiré (jour 1 PaO2:FiO2 = 177 [138­276]; jour 10 = 173 [147­227]), de la compliance (jour 1 = 48 [38­58] mL/cmH2O; jour 10 = 34 [28­42] mL/cmH2O), ainsi que par une fraction d'espace mort estimé très élevée (jour 1 = 0,60 [0,53-0,67]; jour 10 = 0,72 [0,69-0,79]). La mortalité hospitalière était de 25 % globalement, et de 21 % chez les patients avec VMI. La mortalité a atteint 82 % chez les patients agés de ≥ 80 ans. CONCLUSION: Les caractéristiques et le devenir des patients en état critique atteints de la COVID-19 à Montréal étaient semblables à ceux rapportés dans la littérature existante. Nous avons observé un espace mort physiologique augmenté, ce qui appuie l'hypothèse que des lésions vasculaires pulmonaires seraient primordiales dans les lésions pulmonaires induites par la COVID-19.

Validation of the Withdrawal Assessment Tool-1 in Adult Intensive Care Patients.

BACKGROUND: The Withdrawal Assessment Tool-1 (WAT-1) has been validated for assessing iatrogenic withdrawal syndrome in critically ill children receiving mechanical ventilation, but little is known about this syndrome in critically ill adults. OBJECTIVE: To evaluate the validity and reliability of the WAT-1 in critically ill adults. METHODS: A prospective, observational, open-cohort pilot study of critically ill adults receiving mechanical ventilation and regular administration of opioids for at least 72 hours. Patients were assessed for withdrawal twice daily on weekdays and once daily on weekends using the WAT-1 after an opioid weaning episode. The presence of iatrogenic withdrawal syndrome was evaluated once daily using modified Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) criteria. All evaluations were blinded and performed independently. The criterion validity of the WAT-1 and the interrater reliability for WAT-1 and DSM-5 evaluations were determined. RESULTS: During 8 months, 52 adults (median age, 51.5 years) were enrolled. Eight patients (15%) had at least 1 positive assessment during their intensive care unit stay using the DSM-5, compared with 19 patients (37%) using the WAT-1. The overall sensitivity of the WAT-1 was 50%, and its specificity was 65.9%. Agreement between WAT-1 and DSM-5 assessments was poor (κ = 0.102). The interrater reliability for the WAT-1 was 89.1% and for the DSM-5 was 90.1%. CONCLUSION: Despite showing reliability, the WAT-1 is not a valid tool for assessing the presence of iatrogenic withdrawal syndrome in adults.

A systematic review of interventions to facilitate extubation in patients difficult-to-wean due to delirium, agitation, or anxiety and a meta-analysis of the effect of dexmedetomidine.

BACKGROUND: Delirium, agitation, and anxiety may hinder weaning from mechanical ventilation and lead to increased morbidity and healthcare costs. The most appropriate clinical approach to weaning in these contexts remains unclear and challenging to clinicians. The objective of this systematic review was to identify effective and safe interventions to wean patients that are difficult-to-wean from mechanical ventilation due to delirium, agitation, or anxiety. METHODS: A systematic review was performed using MEDLINE, EMBASE, and PubMed. Studies evaluating mechanically ventilated patients deemed difficult-to-wean due to delirium, agitation, or anxiety, and comparing the effects of an intervention with a comparator arm were sought. Time-to-extubation was the primary outcome while the secondary outcome was intensive care unit (ICU) length of stay. RESULTS: From 10,860 studies identified, eight met the inclusion criteria: six studies assessed dexmedetomidine while the remaining two assessed loxapine and biofeedback. Pooled analysis of studies assessing dexmedetomidine showed reduced time-to-extubation (six studies, n = 303) by 10.9 hr compared with controls (95% confidence interval [CI], -15.7 to -6.1; I2 = 68%) and ICU length of stay (four studies, n = 191) by 2.6 days (95% CI, 1.9 to 3.3; I2 = 0%). Nevertheless, the evidence was deemed to be of low quality given the small sample sizes and high heterogeneity. Studies assessing other interventions did not identify improvements compared with controls. Safety assessment was globally poorly reported. CONCLUSIONS: This systematic review and meta-analysis provides low quality evidence to suggest the use of dexmedetomidine in patients deemed difficult-to-wean due to agitation, delirium, or anxiety. Insufficient evidence was found regarding other interventions to provide any recommendation. TRIAL REGISTRATION: PROSPERO (CRD42016042528); registered 15 July, 2016.

RéSUMé: CONTEXTE: Le délirium, l'agitation et l'anxiété peuvent compliquer le sevrage de la ventilation mécanique et aboutir à une augmentation de la morbidité et du coût des soins de santé. L'approche clinique la plus adaptée au sevrage dans ces circonstances n'est pas claire et reste un défi pour les cliniciens. L'objectif de cette étude systématique était d'identifier des interventions efficaces et sécuritaires pour sevrer les patients « difficiles à sevrer ¼ de la ventilation mécanique en raison d'un délirium, d'une agitation ou d'anxiété. MéTHODES: Une revue systématique a été menée en utilisant les bases de données MEDLINE, EMBASE et PubMed. Les études évaluant des patients sous ventilation mécanique jugés difficiles à sevrer en raison d'un délirium, d'une agitation ou d'anxiété, comparant les effets d'une intervention à celle d'un bras comparateur ont été recherchées. Le critère d'évaluation principal a été le délai jusqu'à l'extubation et le critère d'évaluation secondaire a été la durée de séjour en unité de soins intensifs (USI). RéSULTATS: À partir de 10 860 études identifiées, huit satisfaisaient les critères d'inclusion : six études ont évalué la dexmédétomidine tandis que les deux dernières ont évalué la loxapine et le biofeedback. L'analyse groupée des études évaluant la dexmédétomidine a montré une réduction du délai d'extubation (six études, n = 303) de 10,9 heures comparativement aux contrôles (intervalle de confiance [IC] à 95 % : -15,7 à -6,1; I2 = 68 %) et de la durée du séjour en USI (quatre études, n = 191) de 2,6 jours (IC à 95 % : 1,9 à 3,3; I2 = 0 %). Néanmoins, les résultats sont de faible qualité compte tenu de la petite taille des échantillons et d'une grande hétérogénéité. Les études évaluant d'autres interventions n'ont pas identifié d'améliorations par rapport aux contrôles. D'une manière générale, les évaluations de l'innocuité ont été médiocrement décrites. CONCLUSIONS: Cette étude systématique et la méta-analyse procurent une preuve de qualité basse pour suggérer l'utilisation de la dexmédétomidine chez des patients considérés difficiles à sevrer en raison d'un délirium, d'une agitation ou d'anxiété. Les données probantes concernant les autres interventions ont été jugées insuffisantes pour permettre des recommandations quelconques. ENREGISTREMENT DE L'ESSAI CLINIQUE: PROSPERO (CRD42016042528); enregistré le 15 juillet 2016.

Opioid-associated iatrogenic withdrawal in critically ill adult patients: a multicenter prospective observational study.

BACKGROUND: Opioids and benzodiazepines are frequently used in the intensive care unit (ICU). Regular use and prolonged exposure to opioids in ICU patients followed by abrupt tapering or cessation may lead to iatrogenic withdrawal syndrome (IWS). IWS is well described in pediatrics, but no prospective study has evaluated this syndrome in adult ICU patients. The objective of this study was to determine the incidence of IWS caused by opioids in a critically ill adult population. This multicenter prospective cohort study was conducted at two level-1 trauma ICUs between February 2015 and September 2015 and included 54 critically ill patients. Participants were eligible if they were 18 years and older, mechanically ventilated and had received more than 72 h of regular intermittent or continuous intravenous infusion of opioids. For each enrolled patient and per each opioid weaning episode, presence of IWS was assessed by a qualified ICU physician or senior resident according to the 5th edition of Diagnostic and Statistical Manual of Mental Disorders criteria for opioid withdrawal. RESULTS: The population consisted mostly of males (74.1%) with a median age of 50 years (25th-75th percentile 38.2-64.5). The median ICU admission APACHE II score was 22 (25th-75th percentile 12.0-28.2). The overall incidence of IWS was 16.7% (95% CI 6-27). The median cumulative opioid dose prior to weaning was higher in patients with IWS (245.7 vs. 169.4 mcg/kg, fentanyl equivalent). Patients with IWS were also exposed to opioids for a longer period of time as compared to patients without IWS (median 151 vs. 125 h). However, these results were not statistically significant. CONCLUSIONS: IWS was occasionally observed in this very specific population of mechanically ventilated, critically ill ICU patients. Further studies are needed to confirm these preliminary results and identify risk factors.

Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome.

AIM: To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome (ARDS). METHODS: Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of iNO (20 ppm) or nebulized epoprostenol (10 µg/mL) was done in all patients. Thereafter, inhaled milrinone (1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide (iNO) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen (PaO2) were recorded before and after each inhaled therapy administration. RESULTS: The majority of ARDS were of pulmonary cause (n = 13) and pneumonia (n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass (n = 2), smoke inhalation injury (n = 1), thoracic trauma and pulmonary contusions (n = 2) and aspiration (n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and iNO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO2 from baseline was 8.8 mmHg [interquartile range (IQR) = 16.3], 6.0 mmHg (IQR = 18.4), 6 mmHg (IQR = 15.8) and 9.2 mmHg (IQR = 20.2) respectively with iNO, epoprostenol, inhaled milrinone, and iNO added to milrinone. Only iNO and the combination of inhaled milrinone and iNO had a statistically significant effect on PaO2. CONCLUSION: When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS.

Effect of ventilatory variability on occurrence of central apneas.

OBJECTIVE: To compare the influence of 2 ventilation strategies on the occurrence of central apneas. METHODS: This was a prospective, comparative, crossover study with 14 unsedated subjects undergoing weaning from mechanical ventilation in the medical ICU of Hôpital du Sacré-Cœur, Montréal, Québec, Canada. The subjects were ventilated alternately in neurally adjusted ventilatory assist (NAVA) and pressure support ventilation (PSV) modes. Inspiratory flow/time and pressure/time waveforms and diaphragmatic electrical activity were used to detect central apneas. Ventilatory variability and breathing pattern were evaluated in both modes. Breathing patterns just before central apneas, and associations between apneas and sleep patterns (electroencephalogram) were studied. RESULTS: Switching from PSV to NAVA did not change mean minute ventilation, tidal volume, or breathing frequency. However, tidal volume variability, defined as the coefficient of variability (standard error/mean), was significantly greater with NAVA than with PSV (17.2 ± 8 vs 10.3 ± 4, P = .045). NAVA induced a greater decrease in central apneas, compared to PSV (to 0 with NAVA vs 10.5 ± 11 with PSV, P = .005). Central apneas during PSV were detected only during non-rapid-eye-movement sleep. CONCLUSIONS: NAVA was associated with increased ventilatory variability, compared to constant-level PSV. With NAVA the absence of over-assistance during sleep coincided with absence of central apneas, suggesting that load capacity and/or neuromechanical coupling were improved by NAVA and that this improvement decreased or abolished central apneas.

Sleep quality in mechanically ventilated patients: comparison between NAVA and PSV modes.

BACKGROUND: Mechanical ventilation seems to occupy a major source in alteration in the quality and quantity of sleep among patients in intensive care. Quality of sleep is negatively affected with frequent patient-ventilator asynchronies and more specifically with modes of ventilation. The quality of sleep among ventilated patients seems to be related in part to the alteration between the capacities of the ventilator to meet patient demand. The objective of this study was to compare the impact of two modes of ventilation and patient-ventilator interaction on sleep architecture. METHODS: Prospective, comparative crossover study in 14 conscious, nonsedated, mechanically ventilated adults, during weaning in a university hospital medical intensive care unit. Patients were successively ventilated in a random ordered cross-over sequence with neurally adjusted ventilatory assist (NAVA) and pressure support ventilation (PSV). Sleep polysomnography was performed during four 4-hour periods, two with each mode in random order. RESULTS: The tracings of the flow, airway pressure, and electrical activity of the diaphragm were used to diagnose central apneas and ineffective efforts. The main abnormalities were a low percentage of rapid eye movement (REM) sleep, for a median (25th-75th percentiles) of 11.5% (range, 8-20%) of total sleep, and a highly fragmented sleep with 25 arousals and awakenings per hour of sleep. Proportions of REM sleep duration were different in the two ventilatory modes (4.5% (range, 3-11%) in PSV and 16.5% (range, 13-29%) during NAVA (p = 0.001)), as well as the fragmentation index, with 40 ± 20 arousals and awakenings per hour in PSV and 16 ± 9 during NAVA (p = 0.001). There were large differences in ineffective efforts (24 ± 23 per hour of sleep in PSV, and 0 during NAVA) and episodes of central apnea (10.5 ± 11 in PSV vs. 0 during NAVA). Minute ventilation was similar in both modes. CONCLUSIONS: NAVA improves the quality of sleep over PSV in terms of REM sleep, fragmentation index, and ineffective efforts in a nonsedated adult population.

Preliminary evaluation of a new index to predict the outcome of a spontaneous breathing trial.

BACKGROUND: The available predictors of spontaneous-breathing-trial (SBT) success/failure lack accuracy. We devised a new index, the CORE index (compliance, oxygenation, respiration, and effort). OBJECTIVE: To compare the CORE index to the CROP index (compliance, rate, oxygenation, and pressure), airway-occlusion pressure 0.1 s after the start of inspiratory flow (P(0.1)), and rapid shallow breathing index (RSBI) for predicting SBT success/failure in a critical care environment. METHODS: With 47 mechanically ventilated patients recovering from respiratory failure, of various causes, we prospectively examined the SBT success/failure prediction accuracy and calculated receiver operating characteristic curves, sensitivity, specificity, and likelihood ratios of CORE, CROP, P(0.1), and RSBI. RESULTS: The specificities were CORE 0.95, P(0.1) 0.70, CROP 0.70, and RSBI 0.65. The sensitivities were CORE 1.00, CROP 1.00, P(0.1) 0.93, and RSBI 0.89. The areas under the receiver operating characteristic curve were CORE 1.00 (95% CI 0.92-1.00), CROP 0.91 (95% CI 0.79-0.97), P(0.1) 0.81 (95% CI 0.67-0.91), and RSBI 0.77 (95% CI 0.62-0.88). The positive likelihood ratios were CORE 20.0, CROP 3.3, P(0.1) 3.1, and RSBI 2.5. The negative likelihood ratios were CORE 0.0, CROP 0.0, P(0.1) 0.1, and RSBI 0.2. CONCLUSIONS: The CORE index was the most accurate predictor of SBT success/failure.

Patient-ventilator interaction during pressure support ventilation and neurally adjusted ventilatory assist.

OBJECTIVE: To compare the effect of pressure support ventilation and neurally adjusted ventilatory assist on breathing pattern, patient-ventilator synchrony, diaphragm unloading, and gas exchange. Increasing the level of pressure support ventilation can increase tidal volume, reduce respiratory rate, and lead to delayed ventilator triggering and cycling. Neurally adjusted ventilatory assist uses diaphragm electrical activity to control the timing and pressure of assist delivery and is expected to enhance patient-ventilator synchrony. DESIGN: Prospective, comparative, crossover study. SETTING: Adult critical care unit in a tertiary university hospital. PATIENTS: Fourteen nonsedated mechanically ventilated patients (n = 12 with chronic obstructive pulmonary disease). INTERVENTIONS: Patients were ventilated for 10-min periods, using two pressure support ventilation levels (lowest tolerable and +7 cm H2O higher) and two neurally adjusted ventilatory assist levels (same peak pressures and external positive end-expiratory pressure as with pressure support ventilation), delivered in a randomized order. MEASUREMENTS AND MAIN RESULTS: Diaphragm electrical activity, respiratory pressures, air flow, volume, neural and ventilator respiratory rates, and arterial blood gases were measured. Peak pressures were 17 +/- 6 cm H2O and 24 +/- 6 cm H2O and 19 +/- 5 cm H2O and 24 +/- 6 cm H2O with high and low pressure support ventilation and neurally adjusted ventilatory assist, respectively. The breathing pattern was comparable with pressure support ventilation and neurally adjusted ventilatory assist during low assist; during higher assist, larger tidal volumes (p = .003) and lower breathing frequencies (p = .008) were observed with pressure support ventilation. Increasing the assist increased cycling delays only with pressure support ventilation (p = .003). Compared with pressure support ventilation, neurally adjusted ventilatory assist reduced delays of ventilator triggering (p < .001 for low and high assist) and cycling (high assist: p = .004; low assist: p = .04), and abolished wasted inspiratory efforts observed with pressure support ventilation in six subjects. The diaphragm electrical activity and pressure-time product for ventilator triggering were lower with neurally adjusted ventilatory assist (p = .005 and p = .02, respectively; analysis of variance). Arterial blood gases were similar with both modes. CONCLUSIONS: Neurally adjusted ventilatory assist can improve patient-ventilator synchrony by reducing the triggering and cycling delays, especially at higher levels of assist, at the same time preserving breathing and maintaining blood gases.

Variations in pulmonary artery occlusion pressure to estimate changes in pleural pressure.

OBJECTIVE: A readily available assessment of changes in pleural pressure would be useful for ventilator and fluid management in critically ill patients. We examined whether changes in pulmonary artery occlusion pressure (Ppao) adequately reflect respiratory changes in pleural pressure as assessed by changes in intraesophageal balloon pressure (Peso). We studied patients who had a pulmonary catheter and esophageal balloon surrounding a nasogastric tube as part of their care (n=24). We compared changes in Ppao (dPpao) to changes in Peso (dPeso) by Bland-Altman and regression analysis. Adequacy of balloon placement was assessed by performing Mueller maneuvers and adjusting the position to achieve a ratio of dPeso to change in tracheal pressure (dPtr) of 0.85 or higher. This was achieved in only 14 of the 24 subjects. We also compared dCVP to dPeso. The dPpao during spontaneous breaths and positive pressure breaths gave a good estimate of Peso but generally underestimated dPeso (bias=2.2 +8.2 and -3.9 cmH2O for the whole group). The dCVP was not as good a predictor (bias=2.9 +10.3 and -4.6). In patients who have a pulmonary artery catheter in place dPpao gives a lower estimate of changes in pleural pressure and may be more reliable than dPeso. The dCVP is a less reliable predictor than changes in pleural pressure.