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1.
Crit Care ; 26(1): 148, 2022 05 23.
Article in English | MEDLINE | ID: covidwho-1862142

ABSTRACT

BACKGROUND: A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose-response relationship between ketamine and bilirubin levels. METHODS: Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure-effect relationship between ketamine infusion and total bilirubin levels. RESULTS: Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9-2.0] mg/kg/h for 9 [4-18] days. The mixed-effects model revealed a positively correlated infusion duration-effect as well as dose-effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3-7.8] (p = 0.01). CONCLUSIONS: A causally plausible, dose-effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.


Subject(s)
COVID-19 , Ketamine , Propofol , Respiratory Distress Syndrome , Bilirubin , COVID-19/complications , Critical Illness , Humans , Hypnotics and Sedatives/adverse effects , Ketamine/adverse effects , Liver , Respiration, Artificial/adverse effects , Respiratory Distress Syndrome/chemically induced , Retrospective Studies
2.
Trials ; 23(1): 406, 2022 May 16.
Article in English | MEDLINE | ID: covidwho-1846862

ABSTRACT

BACKGROUND: Administration of sedative and opioid medications to patients receiving mechanical ventilatory support in the intensive care unit is a common clinical practice. METHODS: A two-site randomized open-label clinical trial will test the efficacy of self-management of sedative therapy with dexmedetomidine compared to usual care on anxiety, delirium, and duration of ventilatory support after randomization. Secondary objectives are to compare self-management of sedative therapy to usual care on level of alertness, total aggregate sedative and opioid medication exposure, and ventilator-free days up to day 28 after study enrolment. Exploratory objectives of the study are to compare self-management of sedative therapy to usual care on 3- and 6-month post-discharge physical and functional status, psychological well-being (depression, symptoms of post-traumatic stress disorder), health-related quality of life, and recollections of ICU care. ICU patients (n = 190) who are alert enough to follow commands to self-manage sedative therapy are randomly assigned to self-management of sedative therapy or usual care. Patients remain in the ICU sedative medication study phase for up to 7 days as long as mechanically ventilated. DISCUSSION: The care of critically ill mechanically ventilated patients can change significantly over the course of a 5-year clinical trial. Changes in sedation and pain interventions, oxygenation approaches, and standards related to extubation have substantially impacted consistency in the number of eligible patients over time. In addition, the COVID-19 pandemic resulted in mandated extended pauses in trial enrolment as well as alterations in recruitment methods out of concern for study personnel safety and availability of protective equipment. Patient triaging among healthcare institutions due to COVID-19 cases also has resulted in inconsistent access to the eligible study population. This has made it even more imperative for the study team to be flexible and innovative to identify and enrol all eligible participants. Patient-controlled sedation is a novel approach to the management of patient symptoms that may be able to alleviate mechanical ventilation-induced distress without serious side effects. Findings from this study will provide insight into the efficacy of this approach on short- and long-term outcomes in a subset of mechanically ventilated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02819141. Registered on June 29, 2016.


Subject(s)
COVID-19 , Delirium , Dexmedetomidine , Aftercare , Analgesics, Opioid , Anxiety/diagnosis , Anxiety/therapy , Critical Illness , Delirium/diagnosis , Delirium/drug therapy , Delirium/etiology , Dexmedetomidine/adverse effects , Humans , Hypnotics and Sedatives/adverse effects , Intensive Care Units , Pandemics , Patient Discharge , Quality of Life , Randomized Controlled Trials as Topic , Respiration, Artificial/adverse effects , Respiration, Artificial/methods , Ventilators, Mechanical
3.
Br J Clin Pharmacol ; 88(4): 1567-1589, 2022 02.
Article in English | MEDLINE | ID: covidwho-1840337

ABSTRACT

AIMS: Growing evidence suggests an association between the use of sedative-hypnotic medications and risk of dementia. The aim of this study is to examine this association using a meta-analysis approach. METHODS: MEDLINE (PubMed) and Scopus were systematically searched for studies published in English only. The quality of studies was evaluated using the Newcastle-Ottawa scale, and an overall odds ratio was pooled using a random-effects model. RESULTS: A total of 35 articles were included in the analysis. Pooled odds ratios (ORs) for dementia from all records were (OR; 1.33, 95% CI 1.19-1.49) for benzodiazepine (BZD) combined use (Subgroup-1), (OR: 1.46, 95% CI 1.23-1.73) for short-acting BZD use (Subgroup-2), (OR: 1.72, 95% CI 1.48-1.99) for long-acting BZD use (Subgroup-3), (OR: 1.13, 95% CI 0.97-1.32) for BZDs without specification of duration of action (Subgroup-4), (OR: 1.64, 95% CI 1.13-2.38) for the combined BZDs and Z-drugs, (OR: 1.43, 95% CI 1.17-1.74) for Z-drugs only, (OR: 1.14, 95% CI 0.88-1.46) for antidepressant use, (OR: 0.97, 95% CI 0.68-1.39) for antipsychotic use and (OR: 0.98, 95% CI 0.85-1.13) for anticonvulsant use. When sensitivity analysis was performed, association between overall use of BZDs and short-acting BZDs with the increased risk of dementia disappeared after exclusion of studies that were not adjusted for age covariate (OR: 1.2, 95% CI 1.0-1.44) and (OR: 1.22, 95% CI 0.75-2.01), respectively. Adjustment for protopathic bias by introduction of a lag period showed no evidence of increased risk of dementia with the use of BZDs (Subgroup-1) (OR: 1.14, 95% CI 0.82-1.58), Z-drugs (OR: 1.29, 95% CI 0.78-2.13), and combined BZDs and Z-drugs (OR: 1.51, 95% CI 0.91-2.53). Combined use of BZDs and Z-drugs showed more positive association when only studies of non-user design were analysed (OR: 2.75, 95% CI 2.23-3.39). CONCLUSIONS: All the investigated sedative-hypnotics showed no association with increased risk of dementia except for BZDs. However, the observed association with BZDs did not persist after exclusion of studies with potential reverse causation and confounding by indication. Therefore, this association needs to be assessed carefully in future research.


Subject(s)
Dementia , Hypnotics and Sedatives , Antidepressive Agents/therapeutic use , Benzodiazepines/adverse effects , Dementia/chemically induced , Dementia/drug therapy , Dementia/epidemiology , Humans , Hypnotics and Sedatives/adverse effects , Odds Ratio
6.
Pediatr Blood Cancer ; 68(11): e29272, 2021 11.
Article in English | MEDLINE | ID: covidwho-1333028

ABSTRACT

BACKGROUND: Sedation for lumbar punctures (LPs) in pediatric acute lymphoblastic leukemia (ALL) patients has been the standard for decades to reduce pain and anxiety. Recent studies on the potential long-term neurocognitive effects of cumulative propofol exposure have raised concerns about this practice. The recent pandemic introduced additional burdens to patients, with the requirement of a negative COVID-19 test prior to each sedated procedure. PROCEDURE: These factors prompted a quality improvement intervention at our institution where we aimed to reduce postinduction sedated LPs by 50%. Our intervention included patient and family education, followed by a simulation of the procedure for selected patients. Those converted to unsedated LPs were queried for their preference. Comparative cost, clinical time, and LP success rates were collected for sedated and unsedated LPs. RESULTS: Following the intervention, the percentage of LPs performed with sedation dropped from 100% to 48%. All LPs were successful using both techniques. Most patients who experienced the unsedated LP technique, and their guardians, strongly preferred this approach. Unsedated LPs significantly reduced clinical time (169 vs. 83 minutes) for families, decreased expenditures ($5736 reduction per procedure), and improved institutional opportunity cost due to a decrease in last-minute cancelations. CONCLUSION: We have shown that it is feasible to significantly reduce the use of sedation for LPs in patients with ALL, which has the potential to improve health and patient experience at a lower cost.


Subject(s)
Hypnotics and Sedatives/therapeutic use , Pain Management , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Spinal Puncture , Adolescent , Adult , COVID-19/diagnosis , Child , Female , Humans , Hypnotics and Sedatives/adverse effects , Male , Pain Management/adverse effects , Pain Management/methods , Propofol/adverse effects , Propofol/therapeutic use , SARS-CoV-2/isolation & purification , Spinal Puncture/methods , Young Adult
8.
J Anesth ; 35(5): 625-632, 2021 10.
Article in English | MEDLINE | ID: covidwho-1281280

ABSTRACT

PURPOSE: In this retrospective study, we compared inhaled sedation with isoflurane to intravenous propofol in invasively ventilated COVID-19 patients with ARDS (Acute Respiratory Distress Syndrome). METHODS: Charts of all 20 patients with COVID-19 ARDS admitted to the ICU of a German University Hospital during the first wave of the pandemic between 22/03/2020 and 21/04/2020 were reviewed. Among screened 333 days, isoflurane was used in 97 days, while in 187 days, propofol was used for 12 h or more. The effect and dose of these two sedatives were compared. Mixed sedation days were excluded. RESULTS: Patients' age (median [interquartile range]) was 64 (60-68) years. They were invasively ventilated for 36 [21-50] days. End-tidal isoflurane concentrations were high (0.96 ± 0.41 Vol %); multiple linear regression yielded the ratio (isoflurane infusion rate)/(minute ventilation) as the single best predictor. Infusion rates were decreased under ECMO (3.5 ± 1.4 versus 7.1 ± 3.2 ml∙h-1; p < 0.001). In five patients, the maximum recommended dose of propofol of 4 mg∙hour-1∙kg-1ABW was exceeded on several days. On isoflurane compared to propofol days, neuro-muscular blocking agents (NMBAs) were used less frequently (11% versus 21%; p < 0.05), as were co-sedatives (7% versus 31%, p < 0.001); daily opioid doses were lower (720 [720-960] versus 1080 [720-1620] mg morphine equivalents, p < 0.001); and RASS scores indicated deeper levels of sedation (- 4.0 [- 4.0 to - 3.0] versus - 3.0 [- 3.6 to - 2.5]; p < 0.01). CONCLUSION: Isoflurane provided sufficient sedation with less NMBAs, less polypharmacy and lower opioid doses compared to propofol. High doses of both drugs were needed in severely ill COVID-19 patients.


Subject(s)
COVID-19 , Isoflurane , Propofol , Conscious Sedation , Critical Illness , Humans , Hypnotics and Sedatives/adverse effects , Intensive Care Units , Isoflurane/adverse effects , Middle Aged , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
9.
Medicine (Baltimore) ; 100(22): e26240, 2021 Jun 04.
Article in English | MEDLINE | ID: covidwho-1258820

ABSTRACT

RATIONALE: There have been a few reports on the early rehabilitation of patients with coronavirus disease (COVID-19), and none on the effectiveness and adverse events of early mobilization for mechanical ventilation patients (other than COVID-19) during deep sedation. This report indicates that sitting without adverse events is possible in patients with severe COVID-19 pneumonia during deep sedation with muscle relaxation. PATIENT CONCERNS: A 65-year-old man with a history of diabetes mellitus, lacunar infarction, and Parkinson's disease was admitted to a local hospital for pneumonia due to COVID-19. After admission, the patient was managed on a ventilator under deep sedation with muscle relaxants and sedatives. Twelve days after admission, the patient was transferred to our hospital due to his worsening respiratory status. DIAGNOSIS: Pneumonia due to COVID-19 was diagnosed using a polymerase chain reaction-dependent method. INTERVENTIONS: The day following transfer, a physical therapist started passive range of motion training and sitting. OUTCOMES: The period spanning his initial rehabilitation to muscle relaxant medication interruption was 9 days, and he underwent 7 rehabilitation sessions. The patient was unable to sit during only one of the 7 sessions due to pre-rehabilitation hypoxemia. In 5 of the 6 sitting sessions, PaO2/FiO2 transiently decreased but recovered by the time of subsequent blood sampling. The patient's PaCO2 decreased during all sessions. His blood pressure did not drastically decrease in any sitting session, except the first. Sputum excretion via sputum suction increased during sitting, and peak inspiratory pressure did not change. LESSONS: The patient eventually died of pneumonia due to COVID-19. However, sitting during deep sedation with muscle relaxants did not cause any serious adverse events nor did it appear to cause obvious negative respiratory effects.


Subject(s)
COVID-19/rehabilitation , Deep Sedation/methods , Early Ambulation/methods , Sitting Position , Aged , Humans , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Male , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/adverse effects , Range of Motion, Articular , Respiration, Artificial , SARS-CoV-2
10.
Crit Care Med ; 49(9): 1524-1534, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1191508

ABSTRACT

OBJECTIVES: In patients with coronavirus disease 2019-associated acute respiratory distress syndrome, sedatives and opioids are commonly administered which may lead to increased vulnerability to neurologic dysfunction. We tested the hypothesis that patients with coronavirus disease 2019-associated acute respiratory distress syndrome are at higher risk of in-hospital mortality due to prolonged coma compared with other patients with acute respiratory distress syndrome matched for disease severity. DESIGN: Propensity-matched cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: All mechanically ventilated coronavirus disease 2019 patients between March and May 2020 were identified and matched with patients with acute respiratory distress syndrome of other etiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using clinical data obtained from a hospital registry, we matched 114 coronavirus disease 2019 patients to 228 noncoronavirus disease 2019-related acute respiratory distress syndrome patients based on baseline disease severity. Coma was identified using the Richmond Agitation Sedation Scale less than or equal to -3. Multivariable logistic regression and mediation analyses were used to assess the percentage of comatose days, sedative medications used, and the association between coronavirus disease 2019 and in-hospital mortality. In-hospital mortality (48.3% vs 31.6%, adjusted odds ratio, 2.15; 95% CI, 1.34-3.44; p = 0.002), the percentage of comatose days (66.0% ± 31.3% vs 36.0% ± 36.9%, adjusted difference, 29.35; 95% CI, 21.45-37.24; p < 0.001), and the hypnotic agent dose (51.3% vs 17.1% of maximum hypnotic agent dose given in the cohort; p < 0.001) were higher among patients with coronavirus disease 2019. Brain imaging did not show a higher frequency of structural brain lesions in patients with coronavirus disease 2019 (6.1% vs 7.0%; p = 0.76). Hypnotic agent dose was associated with coma (adjusted coefficient, 0.61; 95% CI, 0.45-0.78; p < 0.001) and mediated (p = 0.001) coma. Coma was associated with in-hospital mortality (adjusted odds ratio, 5.84; 95% CI, 3.58-9.58; p < 0.001) and mediated 59% of in-hospital mortality (p < 0.001). CONCLUSIONS: Compared with matched patients with acute respiratory distress syndrome of other etiology, patients with coronavirus disease 2019 received higher doses of hypnotics, which was associated with prolonged coma and higher mortality.


Subject(s)
COVID-19/drug therapy , Coma/etiology , Hospital Mortality , Hypnotics and Sedatives/administration & dosage , Respiration, Artificial , Respiratory Distress Syndrome/etiology , Aged , Analgesics/therapeutic use , Brain/diagnostic imaging , Brain/pathology , COVID-19/complications , COVID-19/mortality , Female , Humans , Hypnotics and Sedatives/adverse effects , Logistic Models , Male , Middle Aged , Neuromuscular Blocking Agents/therapeutic use , Propensity Score , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Retrospective Studies
13.
Encephale ; 46(3S): S116-S118, 2020 Jun.
Article in French | MEDLINE | ID: covidwho-1065050

ABSTRACT

French recommendations have been proposed for psychotropics use and possible adaptations during the SARS-CoV-2 epidemic. Between uncertainties linked to the lack of data and speculations about possible benefits of psychotropics against the coronavirus, we propose here elements allowing to base the pharmacotherapeutic decisions potentially useful in Covid+ patients with psychiatric disorders.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Drug Repositioning , Pandemics , Pneumonia, Viral/drug therapy , Psychotropic Drugs/therapeutic use , Anti-Anxiety Agents/adverse effects , Anti-Anxiety Agents/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Dyspnea/chemically induced , Dyspnea/etiology , Humans , Hypnotics and Sedatives/adverse effects , Hypnotics and Sedatives/therapeutic use , Mental Disorders/drug therapy , Mental Disorders/epidemiology , Pneumonia, Viral/epidemiology , Psychotropic Drugs/adverse effects , Psychotropic Drugs/pharmacology , Respiration/drug effects , Risk Assessment , SARS-CoV-2
14.
Psychosomatics ; 61(5): 544-550, 2020.
Article in English | MEDLINE | ID: covidwho-616923
17.
Am J Emerg Med ; 38(10): 2243.e1-2243.e3, 2020 10.
Article in English | MEDLINE | ID: covidwho-342862

ABSTRACT

We report the first two cases of Coronavirus Disease 2019 (COVID-19) who were receiving intensive care including favipiravir, and were clinically diagnosed with neuroleptic malignant syndrome (NMS) to focus attention on NMS in COVID-19 management. Case 1: A 46-year-old-man with acute respiratory distress syndrome (ARDS) caused by COVID-19 infection was being administered favipiravir. Fentanyl, propofol, and rocuronium were also given. On day 3, midazolam administration was initiated for deep sedation. On day 5, his high body temperature increased to 41.2 °C, creatine kinase level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS was suspected, and supportive therapy was initiated. High-grade fever persisted for 4 days and subsided on day 9. Case 2: A 44-year-old-man with ARDS caused by COVID-19 infection was being treated with favipiravir. On day 5, risperidone was started for delirium. On day 7, his body temperature suddenly increased to 40.8 °C, his CK level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS diagnosis was confirmed, and both, favipiravir and risperidone were discontinued on day 8. On the same day, his CK levels decreased, and his body temperature normalized on day 9. Patients with COVID-19 infection frequently require deep sedation and develop delirium; therefore, more attention should be paid to the development of NMS in patients who are being administered such causative agents. The mechanism underlying the occurrence of NMS in COVID-19 patients treated with favipiravir remains unknown. Therefore, careful consideration of NMS development is necessary in the management of COVID-19 patients.


Subject(s)
Antipsychotic Agents/adverse effects , COVID-19/drug therapy , Hypnotics and Sedatives/adverse effects , Neuroleptic Malignant Syndrome/etiology , Respiratory Distress Syndrome/drug therapy , Adult , Humans , Male , Middle Aged , Respiration, Artificial , Respiratory Distress Syndrome/etiology
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