Pneumococcal meningitis secondary to otitis media in two patients with COVID-19 omicron variant.

BACKGROUND: The SARS-CoV-2 omicron variant produces more symptoms in the upper respiratory tract than in the lower respiratory tract. This form of "common cold" can cause inflammation of the oropharynx and the Eustachian tube, leading to the multiplication of bacteria such as Streptococcus pneumoniae in the oropharynx. Eustachian tube dysfunction facilitates migration of these bacteria to the middle ear, causing inflammation and infection (otitis media), which in turn could lead to further complications such as acute mastoiditis and meningitis. CASE PRESENTATION: In January 2022, during the rapid spread of the omicron variant of the SARS-CoV-2 virus, two patients presented to the emergency room at our hospital complaining of headache and a low level of consciousness. A few days prior to admission, the patients had been diagnosed with COVID-19 based on clinical manifestations of a cold virus, without respiratory failure. Cranial computed tomography revealed signs of bilateral invasion of the middle ear in both cases. Lumbar puncture was compatible with acute bacterial meningitis, and S. pneumoniae was isolated in cerebrospinal fluid in both patients. RT-PCR tests for SARS-CoV-2 were repeated, confirming the presence of the omicron variant in one of the patients. We were unable to confirm the variant in the second patient due to the low viral load in the nasopharyngeal sample obtained at admission. However, the time of diagnosis (i.e., during the peak spread of the omicron variant), strongly suggest the presence of the omicron variant. Both patients were admitted to the intensive care unit and both showed rapid clinical improvement after initiation of antibiotic treatment. CONCLUSIONS: The omicron variant of the SARS-CoV-2 virus can promote the development of otitis media and secondary acute bacterial meningitis. S. pneumoniae is one of the main bacteria involved in this process.

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

Non-invasive oxygenation support in acutely hypoxemic COVID-19 patients admitted to the ICU: a multicenter observational retrospective study.

BACKGROUND: Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. METHODS: In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. RESULTS: Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula (n = 439) and non-invasive mechanical ventilation (n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks (n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58-0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80-1.83] for non-invasive mechanical ventilation. CONCLUSION: In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy.

Prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with COVID-19 in Europe: Initial report of the international RISC-19-ICU prospective observational cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. METHODS: Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. FINDINGS: As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5-21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80-148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3·2, 95% CI [1·7-6·0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0·35, 0·34), CRP, creatinine, troponin, d-dimer, lactate, neutrophil count, P/F-ratio diverged within the first seven days (p<0·01). On a multivariable Cox proportional-hazard regression model at admission, creatinine, d-dimer, lactate, potassium, P/F-ratio, alveolar-arterial gradient, and ischemic heart disease were independently associated with ICU-mortality. INTERPRETATION: The European RISC-19-ICU cohort demonstrates a moderate mortality of 24% in critically ill patients with COVID-19. Despite high ARDS severity, mechanical ventilation incidence was low and associated with more rescue therapies. In contrast to risk factors in hospitalized patients reported in other studies, the main mortality predictors in these critically ill patients were markers of oxygenation deficit, renal and microvascular dysfunction, and coagulatory activation. Elevated risk of bloodstream infections underscores the need to exercise caution with off-label therapies.

Pain distress: the negative emotion associated with procedures in ICU patients.

PURPOSE: The intensity of procedural pain in intensive care unit (ICU) patients is well documented. However, little is known about procedural pain distress, the psychological response to pain. METHODS: Post hoc analysis of a multicenter, multinational study of procedural pain. Pain distress was measured before and during procedures (0-10 numeric rating scale). Factors that influenced procedural pain distress were identified by multivariable analyses using a hierarchical model with ICU and country as random effects. RESULTS: A total of 4812 procedures were recorded (3851 patients, 192 ICUs, 28 countries). Pain distress scores were highest for endotracheal suctioning (ETS) and tracheal suctioning, chest tube removal (CTR), and wound drain removal (median [IQRs] = 4 [1.6, 1.7]). Significant relative risks (RR) for a higher degree of pain distress included certain procedures: turning (RR = 1.18), ETS (RR = 1.45), tracheal suctioning (RR = 1.38), CTR (RR = 1.39), wound drain removal (RR = 1.56), and arterial line insertion (RR = 1.41); certain pain behaviors (RR = 1.19-1.28); pre-procedural pain intensity (RR = 1.15); and use of opioids (RR = 1.15-1.22). Patient-related variables that significantly increased the odds of patients having higher procedural pain distress than pain intensity were pre-procedural pain intensity (odds ratio [OR] = 1.05); pre-hospital anxiety (OR = 1.76); receiving pethidine/meperidine (OR = 4.11); or receiving haloperidol (OR = 1.77) prior to the procedure. CONCLUSIONS: Procedural pain has both sensory and emotional dimensions. We found that, although procedural pain intensity (the sensory dimension) and distress (the emotional dimension) may closely covary, there are certain factors than can preferentially influence each of the dimensions. Clinicians are encouraged to appreciate the multidimensionality of pain when they perform procedures and use this knowledge to minimize the patient's pain experience.

Cardiac function during weaning failure: the role of diastolic dysfunction.

BACKGROUND: Cardiac dysfunction is a common cause of weaning failure. Weaning shares some similarities with a cardiac stress test and may challenge active phases of the cardiac cycle-like ventricular contractility and relaxation. This study aimed at assessing systolic and diastolic function during the weaning process and scrutinizing their dynamics during weaning trials. METHODS: Echocardiography was performed during baseline ventilator settings to assess cardiac function at the initiation of the weaning process and at the start and the end of consecutive weaning trials (performed at day-1, day-2, and before extubation if applicable) to explore the evolution of left ventricle contractility and relaxation in a subset of patients. RESULTS: Among 67 patients included, weaning was prolonged (≥ 7 days) in 18 (27%) patients and short (< 7 days) in 49 (73%). Prevalence of systolic dysfunction and isolated diastolic dysfunction before the initiation of weaning process were 37 and 17%, respectively. Isolated diastolic dysfunction was more frequent in patients with prolonged weaning as compared to their counterparts. Thirty-one patients were explored by echocardiography during consecutive weaning trials. An increase in filling pressures with an alteration of ventricular relaxation (as assessed by a decrease in tissue Doppler early mitral diastolic wave velocity) was found during failed weaning trials. CONCLUSIONS: Isolated diastolic dysfunction was associated with a prolongation of weaning. Increased filling pressures with left ventricle relaxation impairment may be a key mechanism of weaning trial failure.

End-inspiratory pause prolongation in acute respiratory distress syndrome patients: effects on gas exchange and mechanics.

BACKGROUND: End-inspiratory pause (EIP) prolongation decreases dead space-to-tidal volume ratio (Vd/Vt) and PaCO2. We do not know the physiological benefits of this approach to improve respiratory system mechanics in acute respiratory distress syndrome (ARDS) patients when mild hypercapnia is of no concern. METHODS: The investigation was conducted in an intensive care unit of a university hospital, and 13 ARDS patients were included. The study was designed in three phases. First phase, baseline measurements were taken. Second phase, the EIP was prolonged until one of the following was achieved: (1) EIP of 0.7 s; (2) intrinsic positive end-expiratory pressure ≥1 cmH2O; or (3) inspiratory-expiratory ratio 1:1. Third phase, the Vt was decreased (30 mL every 30 min) until PaCO2 equal to baseline was reached. FiO2, PEEP, airflow and respiratory rate were kept constant. RESULTS: EIP was prolonged from 0.12 ± 0.04 to 0.7 s in all patients. This decreased the Vd/Vt and PaCO2 (0.70 ± 0.07 to 0.64 ± 0.08, p < 0.001 and 54 ± 9 to 50 ± 8 mmHg, p = 0.001, respectively). In the third phase, the decrease in Vt (from 6.3 ± 0.8 to 5.6 ± 0.8 mL/Kg PBW, p < 0.001) allowed to decrease plateau pressure and driving pressure (24 ± 3 to 22 ± 3 cmH2O, p < 0.001 and 13.4 ± 3.6 to 10.9 ± 3.1 cmH2O, p < 0.001, respectively) and increased respiratory system compliance from 29 ± 9 to 32 ± 11 mL/cmH2O (p = 0.001). PaO2 did not significantly change. CONCLUSIONS: Prolonging EIP allowed a significant decrease in Vt without changes in PaCO2 in passively ventilated ARDS patients. This produced a significant decrease in plateau pressure and driving pressure and significantly increased respiratory system compliance, which suggests less overdistension and less dynamic strain.

Aerosol therapy in intensive and intermediate care units: prospective observation of 2808 critically ill patients.

PURPOSE: Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice. METHODS: Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries. All aerosols delivered to patients breathing spontaneously, ventilated invasively or noninvasively (NIV) were recorded, and drugs, devices, ventilator settings, circuit set-up, humidification and side effects were noted. RESULTS: A total of 9714 aerosols were administered to 678 of the 2808 admitted patients (24 %, CI95 22-26 %), whereas only 271 patients (10 %) were taking inhaled medication before admission. There were large variations among centers, from 0 to 57 %. Among intubated patients 22 % (n = 262) received aerosols, and 50 % (n = 149) of patients undergoing NIV, predominantly (75 %) inbetween NIV sessions. Bronchodilators (n = 7960) and corticosteroids (n = 1233) were the most frequently delivered drugs (88 % overall), predominantly but not exclusively (49 %) administered to patients with chronic airway disease. An anti-infectious drug was aerosolized 509 times (5 % of all aerosols) for nosocomial infections. Jet-nebulizers were the most frequently used device (56 %), followed by metered dose inhalers (23 %). Only 106 (<1 %) mild side effects were observed, despite frequent suboptimal set-ups such as an external gas supply of jet nebulizers for intubated patients. CONCLUSIONS: Aerosol therapy concerns every fourth critically ill patient and one-fifth of ventilated patients.

Fentanyl as pre-emptive treatment of pain associated with turning mechanically ventilated patients: a randomized controlled feasibility study.

PURPOSE: To compare pain incidence and changes in pain scores with fentanyl versus placebo as pre-emptive treatment during turning and 30 min post-turning in mechanically ventilated critically ill patients. METHODS: We performed a randomized, double-blind, parallel-group, placebo-controlled clinical trial in the intensive care unit of a university hospital. Seventy-five mechanically ventilated patients were randomized to an intervention group (fentanyl) or a control group (placebo). Patients in the intervention group received 1 µg/kg (medical patients) or 1.5 µg/kg (surgical patients) of fentanyl 10 min before turning. Pain indicators were assessed using the behavioral pain scale. Safety was assessed by determining the frequency and severity of pre-defined adverse events. Pain was evaluated at rest (T0), at turn start and end (T1 and T2) and at 5, 15 and 30 min post-turning (T3, T4 and T5). RESULTS: The two groups had similar baseline characteristics. The area under the curve for BPS values was significantly smaller in the fentanyl group than in the control group [median and interquartile range (IQR): 132 (108-150) vs. 147 (125-180); p = 0.016, respectively]. Nineteen non-serious adverse events were recorded in 14 patients, with no significant between-group differences (23 % fentanyl group vs. 14 % control group; p = 0.381). CONCLUSIONS: These results suggest an intravenous bolus of fentanyl of 1 µg/kg for medical patients or 1.5 µg/kg for surgical patients reduces the incidence of turning-associated pain in critically ill patients on mechanical ventilation. ClinicalTrials.gov: NCT 01950000.

Delirium and Circadian Rhythm of Melatonin During Weaning From Mechanical Ventilation: An Ancillary Study of a Weaning Trial.

BACKGROUND: Delirium is frequent in patients in the ICU, but its association with the outcome of weaning from mechanical ventilation has not been assessed. Circadian rhythm alteration may favor delirium. In the current study, we assessed the impact of delirium during weaning and associated alterations in the circadian rhythm of melatonin excretion. METHODS: This was a substudy of 70 participants of the B-type Natriuretic Peptide for the Fluid Management of Weaning trial, comparing two fluid management strategies during weaning. Patients with or without delirium (as assessed using the Confusion Assessment Method for the ICU) were compared in terms of baseline characteristics and outcomes and the circadian rhythm of melatonin excretion using the 24-h excretion of its urinary metabolite 6-sulfatoxymelatonin (aMT6s). RESULTS: Among the 70 patients included, 43 (61.4%) experienced delirium at the initiation of weaning. Delirium at the initiation of weaning was associated with more alcohol consumption, a greater severity of illness, and medication use before weaning (including neuromuscular blockade, antibiotics, sedatives, and narcotics). Delirium at the initiation of weaning was associated with more respiratory and neurologic complications and a reduced probability of successful extubation (Cox multivariate model hazard ratio of successful extubation = 0.54; 95% CI, 0.30-0.95; P = .03). Delirium was also associated with a significant reduction in peak, mean, amplitude, and total values of aMT6s urinary excretion during the first 24 h of weaning (general linear model F statistic = 5.81, P = .019). CONCLUSIONS: Delirium is frequent at the initiation of ventilator weaning. It is associated with a prolongation of weaning and an alteration in the circadian rhythm of melatonin excretion. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00473148; URL: www.clinicaltrials.gov.

Postoperative Discomfort After Abdominal Surgery: An Observational Study.

PURPOSE: Patients who have surgery may experience distress in the following days. Although postoperative distress is a common experience, few studies have analyzed these patient complaints in-depth. The purpose of the present study was to analyze the potential causes of patients' discomfort after abdominal surgery. DESIGN: This was a prospective and observational study. METHODS: Patients (N = 131) were asked to rate their discomfort twice using a list of nine items in the first 6 to 8 hours after surgery and at 24 hours after its completion. Participants were asked to score intensity from 0 (absent) to 10 (unbearable). FINDINGS: The main causes of discomfort at 24 hours were pain (82%), movement restriction (79%), and dry mouth (70%). These items also had the highest scores (by gender, women scored higher than did men in insomnia, dry mouth, and abdominal distension). No significant differences were observed between patients who had undergone open or laparoscopic surgery. CONCLUSION: It was concluded that pain, movement restriction, and dry mouth were the most disturbing causes of discomfort. Therefore, symptoms other than pain should be considered to improve the well-being of patients after abdominal surgery.

Echocardiographic detection of transpulmonary bubble transit during acute respiratory distress syndrome.

BACKGROUND: Transpulmonary bubble transit (TPBT) detected with contrast echocardiography is reported as a sign of intrapulmonary shunt during cirrhosis or exercise in healthy humans. However, its physiological meaning is not clear during acute respiratory distress syndrome (ARDS). Our aim was to determine the prevalence, significance, and prognosis of TPBT detection during ARDS. METHODS: This was a prospective observational study in an academic medical intensive care unit in France. Two hundred and sixteen consecutive patients with moderate-to-severe ARDS underwent transesophageal echocardiography with modified gelatine contrast. Moderate-to-large TPBT was defined as right-to-left passage of at least ten bubbles through a pulmonary vein more than three cardiac cycles after complete opacification of the right atrium. Patients with intra-cardiac shunt through patent foramen ovale were excluded. RESULTS: The prevalence of moderate-to-large TPBT was 26% (including 42 patients with moderate and 15 with large TPBT). Patients with moderate-to-large TPBT had higher values of cardiac index and heart rate as compared to those without TPBT. There was no significant difference in PaO2/FIO2 ratio between groups, and TPBT was not influenced by end-expiratory positive pressure level in 93% of tested patients. Prevalence of septic shock was higher in the group with moderate-to-large TPBT. Patients with moderate-to-large TPBT had fewer ventilator-free days and intensive care unit-free days within the first 28 days, and higher in-hospital mortality as compared to others. CONCLUSIONS: Moderate-to-large TPBT was detected with contrast echocardiography in 26% of patients with ARDS. This finding was associated with a hyperdynamic and septic state, but did not influence oxygenation.

A randomized controlled trial of fentanyl in the pre-emptive treatment of pain associated with turning in patients under mechanical ventilation: research protocol.

AIM: To compare the effectiveness and safety of fentanyl with placebo as pre-emptive treatment for pain associated with turning in patients in intensive care units. BACKGROUND: Turning is frequently a painful procedure in this setting. Pre-emptive administration of supplementary analgesia may help decrease this pain. However, medical literature on pre-emptive analgesia in these patients is scarce. DESIGN: A randomized, double-blind, controlled clinical trial. METHODS: This study will assess the benefits and risks of pre-emptive analgesia with fentanyl compared with placebo on turning-associated pain. Eighty patients will be recruited from among those older than 18 years and needing mechanical ventilation for at least 24 hours. Pain intensity will be assessed using the Behavioral Pain Scale. Primary outcome will be pain intensity between the baseline and 30 minutes after turning, measured by the area under the curve of the pain scale scores. Secondary outcomes will be the usefulness of physiological parameters and the Bispectral Index to measure pain and the safety of pre-emptive fentanyl in turning. The study protocol was approved in February 2011. DISCUSSION: If pre-emptive fentanyl is more effective than placebo and reasonably safe, the results of the current study may change nursing attitude in managing turning in critically ill patients. As a consequence, pain may be decreased during this nursing procedure.