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1.
FASEB J ; 36(8): e22481, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2018110

ABSTRACT

Sedatives/anesthetics are important medical tools to facilitate medical care and increase patients' comfort. Increasingly, there is recognition that sedatives/anesthetics can modulate immune functions. Toll-like receptors (TLRs) are major pattern recognition receptors involved in the recognition of microbial components. TLR7 recognizes single-strand RNA virus such as influenza and SARS-CoV2 viruses and initiates interferon (IFN) responses. IFN production triggered by TLR7 stimulation is a critical anti-viral response. For example, patients with TLR7 variants including loss-of- function variants were associated with severe COVID-19. Taken together, it is important to determine if sedatives/anesthetics mitigate TLR7 function. We have previously showed that TLR7-mediated activation was not affected by volatile anesthetics. However, we found that propofol attenuated TLR7 activation among intravenous sedatives in the reporter assay. TLR7 agonist R837 stimulation increased TNF-α, IL-1ß, IL-6, IL-10, and IFN-ß mRNA levels in bone marrow-derived dendritic cells, while these levels were attenuated by propofol. Our murine lung slice experiments showed that propofol attenuated IFN production. R837 increased IFN-ß expression in the lungs, and propofol attenuated IFN-ß expression in an in vivo model of R837 intranasal instillation. We also found that propofol directly bound to and hindered its association of TLR7 with MyD88. Our analysis using fropofol, propofol derivative showed that the hydroxyl group in propofol was important for propofol-TLR7 interaction.


Subject(s)
COVID-19 , Propofol , Animals , Dendritic Cells , Humans , Hypnotics and Sedatives/pharmacology , Imiquimod , Interferon-alpha/metabolism , Interferon-beta/metabolism , Mice , Propofol/analogs & derivatives , Propofol/pharmacology , RNA, Viral/metabolism , SARS-CoV-2 , Toll-Like Receptor 7
2.
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
3.
JPEN J Parenter Enteral Nutr ; 46(5): 1149-1159, 2022 07.
Article in English | MEDLINE | ID: covidwho-1694689

ABSTRACT

BACKGROUND: Little is known about metabolic and nutrition characteristics of patients with coronavirus disease 2019 (COVID-19) and persistent critical illness. We aimed to compare those characteristics in patients with PCI and COVID-19 and patients without COVID-19 infection (non-CO)-primarily, their energy balance. METHODS: This is a prospective observational study including two consecutive cohorts, defined as needing intubation for >10 days. We collected demographic data, severity scores, nutrition variables, length of stay, and mortality. RESULTS: Altogether, 104 patients (52 per group) were included (59 ± 14 years old [mean ± SD], 75% men) between July 2019 and May 2020. SAPSII, Nutrition Risk Screening (NRS) score, proportion of obese patients, duration of intubation (18.2 ± 11.7 days), and mortality rates were similar. Patients with COVID-19 (vs non-CO) had lower SOFA scores (P = 0.013) and more frequently needed prone position (P < 0.0001) and neuromuscular blockade (P < 0.0001): lengths of ICU (P = 0.03) and hospital stays were shorter (P < 0.0001). Prescribed energy targets were below those of the ICU protocol. The energy balance of patients with COVID-19 was significantly more negative after day 10. Enteral nutrition (EN) started earlier (P < 0.0001). During the first 10 days, COVID-19 patients received more lipid (propofol sedation) and less protein. Higher admission C-reactive protein (P = 0.002) decreased faster (P < 0.001). Whereas intestinal function was characterized by constipation in both groups during the first 10 days, diarrhea was less common in patients with COVID-19 thereafter. CONCLUSION: Compared with non-CO patients, COVID-19 patients were not more obese, had lower SOFA scores, and were fed more rapidly with EN, because of a more normal gastrointestinal function possibly due to fewer non-respiratory organ failures: their energy balances were more negative after the first 10 days. Propofol sedation reduced protein delivery.


Subject(s)
COVID-19 , Percutaneous Coronary Intervention , Propofol , Aged , COVID-19/therapy , Critical Illness/therapy , Energy Intake , Female , Humans , Intensive Care Units , Male , Middle Aged , Obesity/complications , Obesity/therapy
4.
Am J Emerg Med ; 54: 328.e1-328.e2, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1514111

ABSTRACT

BACKGROUND: Status Epilepticus is the most common non-traumatic neurologic emergency in childhood. Current algorithms prioritize the use of benzodiazepines as first line treatment followed by Levetiracetam or Valproic Acid, possibly Fosphenytoin and eventually high dose Propofol and intubation. CASE REPORT: A 9-month old girl was brought to the emergency department with a continuous seizure involving the right upper and lower extremity for 45 min prior to arrival. Patient received a dose of rectal Diazepam, intramuscular Midazolam, 2 doses of Lorazepam, Levetiracetam, Fosphenytoin and 2 additional doses of Lorazepam. The seizure remained refractory and generalized. In anticipation of intubation, and because of its action on the NMDA receptor, Ketamine (1 mg/kg IV) was administered. The clonic movements and eye deviations stopped. Patient was intubated for airway protection, sedated with Propofol, then admitted to the PICU. EEG showed no evidence of a seizure pattern. Labs (CBC, CMP, COVID) were unremarkable except for WBC 24.5, blood glucose of 346 and CO2 of 17 with normal anion gap. Urinalysis showed a urinary tract infection. Patient was at her baseline on 1 week post-discharge re-evaluation. Ketamine theoretically may abort seizures through blockade of NMDA receptors which are unregulated in status epilepticus. To date, no randomized controlled trials have been reported. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ketamine may have a role in treating status epilepticus. It may be considered for induction for rapid sequence intubation and possibly as a third or fourth line agent in refractory cases.


Subject(s)
COVID-19 , Ketamine , Propofol , Status Epilepticus , Aftercare , Anticonvulsants/therapeutic use , Female , Humans , Infant , Ketamine/adverse effects , Levetiracetam , Lorazepam/therapeutic use , Patient Discharge , Propofol/therapeutic use , Seizures/drug therapy , Status Epilepticus/drug therapy
5.
Respir Med ; 189: 106667, 2021.
Article in English | MEDLINE | ID: covidwho-1487955

ABSTRACT

PURPOSE: Deep sedation is sometimes needed in acute respiratory distress syndrome. Ketamine is a sedative that has been shown to have analgesic and sedating properties without having a detrimental impact on hemodynamics. This pharmacological profile makes ketamine an attractive sedative, potentially reducing the necessity for other sedatives and vasopressors, but there are no studies evaluating its effect on these medications in patients requiring deep sedation for acute respiratory distress syndrome. MATERIALS AND METHODS: This is a retrospective, observational study in a single center, quaternary care hospital in southeast Texas. We looked at adults with COVID-19 requiring mechanical ventilation from March 2020 to September 2020. RESULTS: We found that patients had less propofol requirements at 72 h after ketamine initiation when compared to 24 h (median 34.2 vs 54.7 mg/kg, p = 0.003). Norepinephrine equivalents were also significantly lower at 48 h than 24 h after ketamine initiation (median 38 vs 62.8 mcg/kg, p = 0.028). There was an increase in hydromorphone infusion rates at all three time points after ketamine was introduced. CONCLUSIONS: In this cohort of patients with COVID-19 ARDS who required mechanical ventilation receiving ketamine we found propofol sparing effects and vasopressor requirements were reduced, while opioid infusions were not.


Subject(s)
COVID-19/epidemiology , Deep Sedation , Hypnotics and Sedatives/administration & dosage , Ketamine/administration & dosage , Respiration, Artificial , Respiratory Distress Syndrome/epidemiology , Adult , Aged , Aged, 80 and over , Analgesics, Opioid/therapeutic use , COVID-19/therapy , Drug Utilization/statistics & numerical data , Female , Humans , Hydromorphone/therapeutic use , Male , Middle Aged , Norepinephrine/therapeutic use , Propofol/therapeutic use , Respiratory Distress Syndrome/therapy , Retrospective Studies , Texas/epidemiology
6.
Medicina (Kaunas) ; 57(10)2021 Oct 16.
Article in English | MEDLINE | ID: covidwho-1480866

ABSTRACT

Background and Objectives: Early postoperative recovery after surgery is a key point for patients' safety and comfort. Moreover, operating room turnover depends on recovery time. Our aim was to assess which method of remifentanil administration, manual (MI) or target-controlled infusion (TCI), could reduce patient time in recovery room. In this study, patients' recovery times were registered and compared among the groups. Materials and Methods: We enrolled 31 morbidly obese patients in this prospective study. All of them had undergone bariatric surgery at the Hospital of Lithuanian University of Health Sciences Kauno Klinikos in 2020. Sevoflurane/remifentanil anaesthesia was performed for all patients. The patients were randomly assigned to the manual infusion (MI) (control group) or target-controlled infusion (TCI) group for the method of the administration of remifentanil. While the patients were waking up after the surgery, we recorded spontaneous breathing and airway reflexes recovery time, time of extubation, eye opening, recovery of orientation and beginning of the following oral command. For the TCI group, we also documented remifentanil concentrations in the blood (automatic infusion pump). Results: Patients did not differ in demographic values and duration of remifentanil infusion. We found that remifentanil consumption in the TCI group was lower, p = 0.02. Despite lower remifentanil consumption in the TCI group patients, they demonstrated longer total recovery time than the control group patiens: 14 (12-20) vs. 10 (6-16), p = 0.001. Conclusions: The study showed that, upon comparing the TCI method with MI, manual infusion produced better results in postoperative patient recovery. Additionally, higher doses of remifentanil were consumed using MI. In conclusion, the dosage recommended by highly qualified anaesthesiologists is favourable for morbidly obesity patients when compared to the TCI method.


Subject(s)
Bariatric Surgery , Obesity, Morbid , Propofol , Anesthetics, Intravenous , Humans , Obesity, Morbid/surgery , Piperidines , Prospective Studies , Remifentanil
9.
Ann Pharmacother ; 56(6): 637-644, 2022 06.
Article in English | MEDLINE | ID: covidwho-1390445

ABSTRACT

BACKGROUND: Patients with SARS-CoV-2 infection could develop severe disease requiring critical care admission. Case reports indicated high incidence of hypertriglyceridemia (HTG) in critically ill patients infected with SARS-CoV-2, which might be related to the drugs. OBJECTIVE: We sought to determine the risk factors associated with HTG in this population and to investigate the relationship between HTG and lipase. METHODS: A retrospective observational study was conducted at our hospital between March 1 and June 30, 2020. Patients were included if they were ≥18 years old, admitted to the intensive care unit (ICU), tested positive for SARS-CoV-2, and had triglycerides (TG) checked during their hospital stay. RESULTS: Of the 111 critically ill patients, 103 patients were included. Males comprised 88.3% of the sample. The median TG at baseline was 197.4 (IQR: 139.8-283) mg/dL. The lipase median level at baseline was 23.00 (IQR: 0.00-69.50) IU/L. The results of the mixed-effects logistic regression analysis indicated that patient-level variables, favipiravir use, blood glucose level, and propofol use were significantly associated with HTG. There was no relationship between lipase and TG levels over time. Furthermore, TG concentrations over time showed a similar trend to inflammatory markers. CONCLUSION AND RELEVANCE: The incidence of clinically significant HTG was high and was associated with propofol and favipiravir use. HTG might reflect the high inflammatory state in these patients. Clinicians should look at the full picture before changing therapies based only on HTG. Our findings need to be replicated in a larger prospective study.


Subject(s)
COVID-19 , Hypertriglyceridemia , Adult , COVID-19/complications , COVID-19/epidemiology , Critical Illness/therapy , Female , Humans , Hypertriglyceridemia/complications , Hypertriglyceridemia/epidemiology , Intensive Care Units , Lipase , Male , Propofol , Retrospective Studies , SARS-CoV-2 , Triglycerides
10.
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
11.
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
12.
Ann Pharmacother ; 56(1): 5-15, 2022 01.
Article in English | MEDLINE | ID: covidwho-1228971

ABSTRACT

BACKGROUND: Propofol is commonly used to achieve ventilator synchrony in critically ill patients with coronavirus disease 2019 (COVID-19), yet its safety in this patient population is unknown. OBJECTIVE: To evaluate the safety, in particular the incidence of hypertriglyceridemia, of continuous infusion propofol in patients with COVID-19. METHODS: This was a retrospective study at 1 academic medical center and 1 affiliated teaching hospital in New York City. Adult, critically ill patients with COVID-19 who received continuous infusion propofol were included. Patients who received propofol for <12 hours, were transferred from an outside hospital while on mechanical ventilation, or did not have a triglyceride concentration obtained during the infusion were excluded. RESULTS: A total of 252 patients were included. Hypertriglyceridemia (serum triglyceride concentration ≥ 400 mg/dL) occurred in 38.9% of patients after a median cumulative dose of 4307 mg (interquartile range [IQR], 2448-9431 mg). The median time to triglyceride elevation was 3.8 days (IQR, 1.9-9.1 days). In the multivariable regression analysis, obese patients had a significantly greater odds of hypertriglyceridemia (odds ratio = 1.87; 95% CI = 1.10, 3.21). There was no occurrence of acute pancreatitis. The incidence of possible propofol-related infusion syndrome was 3.2%. CONCLUSION AND RELEVANCE: Hypertriglyceridemia occurred frequently in patients with COVID-19 who received propofol but did not lead to acute pancreatitis. Elevated triglyceride concentrations occurred more often and at lower cumulative doses than previously reported in patients without COVID-19. Application of these data may aid in optimal monitoring for serious adverse effects of propofol in patients with COVID-19.


Subject(s)
COVID-19 , Pancreatitis , Propofol , Acute Disease , Adult , Humans , Intensive Care Units , Propofol/adverse effects , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
16.
Heart Surg Forum ; 24(1): E019-E021, 2021 01 14.
Article in English | MEDLINE | ID: covidwho-1079393

ABSTRACT

Pneumonia caused by coronavirus disease 2019 (COVID-19) is a highly contagious disease. Unfortunately, research on extracorporeal membrane oxygenation (ECMO) assisted treatments for patients with COVID-19 infection is limited. In this case study, a patient who was in late pregnancy (35+2 weeks of pregnancy) and suffering from severe COVID-19 was extremely irritable during ECMO-assisted treatment after she underwent a cesarean section. Her Richmond Agitation Sedation Scale (RASS) score reached +3. Nevertheless, the patient successfully was treated with a continuous single/combined application of propofol, midazolam, dexmedetomidine, hibernation mixture, and other drugs for several days (maintaining RASS -2 to -4) and provided with anti-infection, mechanical ventilation, nutritional support, fluid balance under hemodynamic monitoring, liver support, and other organ function support treatments. ECMO-assisted sedation strategy for patients was introduced and discussed in this case to provide a certain reference for the clinical diagnosis and treatment of such patients.


Subject(s)
COVID-19/therapy , Cesarean Section , Dexmedetomidine/administration & dosage , Extracorporeal Membrane Oxygenation , Hypnotics and Sedatives/administration & dosage , Midazolam/administration & dosage , Propofol/administration & dosage , Combined Modality Therapy , Female , Fluid Therapy , Humans , Monitoring, Physiologic , Nutritional Support , Pregnancy , Respiration, Artificial , SARS-CoV-2
18.
Prim Care Companion CNS Disord ; 22(4)2020 Jul 16.
Article in English | MEDLINE | ID: covidwho-654929

ABSTRACT

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.


Subject(s)
Coronavirus Infections/therapy , Deprescriptions , Dexmedetomidine/therapeutic use , Emergence Delirium/diagnosis , Hypnotics and Sedatives/therapeutic use , Pneumonia, Viral/therapy , Respiration, Artificial/methods , Substance Withdrawal Syndrome/diagnosis , Adult , Analgesics, Opioid/therapeutic use , Benzodiazepines/therapeutic use , Betacoronavirus , COVID-19 , Emergence Delirium/therapy , Humans , Male , Neurologic Examination , Pandemics , Practice Guidelines as Topic , Propofol/therapeutic use , SARS-CoV-2 , Substance Withdrawal Syndrome/therapy
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