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SARS-CoV-2 infection results in a spectrum of outcomes from no symptoms to widely varying degrees of illness to death. A better understanding of the immune response to SARS-CoV-2 infection and subsequent, often excessive, inflammation may inform treatment decisions and reveal opportunities for therapy. We studied immune cell subpopulations and their associations with clinical parameters in a cohort of 26 patients with COVID-19. Following informed consent, we collected blood samples from hospitalized patients with COVID-19 within 72 h of admission. Flow cytometry was used to analyze white blood cell subpopulations. Plasma levels of cytokines and chemokines were measured using ELISA. Neutrophils undergoing neutrophil extracellular traps (NET) formation were evaluated in blood smears. We examined the immunophenotype of patients with COVID-19 in comparison to that of SARS-CoV-2 negative controls. A novel subset of pro-inflammatory neutrophils expressing a high level of dual endothelin-1 and VEGF signal peptide-activated receptor (DEspR) at the cell surface was found to be associated with elevated circulating CCL23, increased NETosis, and critical-severity COVID-19 illness. The potential to target this subpopulation of neutrophils to reduce secondary tissue damage caused by SARS-CoV-2 infection warrants further investigation. [ABSTRACT FROM AUTHOR]

Dear Editor, We read with interest the multicenter, randomized, double-blind, placebo-controlled trial conducted by Santer and colleagues examining midodrine administration to expedite weaning of intravenous vasopressor medications [[1]]. In a heterogeneous cohort of 132 critically ill patients enrolled in three centers over 81 months, the investigators concluded midodrine administration (20 mg every 8 h) was ineffective at hastening time to discontinuation of single intravenous vasopressor medication compared to placebo (23.5 vs. 22.5 h; I p i = 0.62), and caused significantly more bradycardia (7.6% vs. 0%; I p i = 0.02). We thank Santer et al. for their report, but wonder if their conclusions would be better framed as "midodrine at a fixed-dose among patients receiving single vasopressor therapy was not effective at reducing the time to pressor discontinuation"?. [Extracted from the article]

Study Objective: High‐dose intravenous vitamin C is a potential treatment option for patients with sepsis and may interfere with point‐of‐care (POC) blood glucose (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis affected POC BG level results. Design: Prospective observational pilot study. Setting: Intensive care unit in a large academic tertiary care medical center. Patients: Five consecutive critically ill adults hospitalized between April 1 and June 1, 2017, who received two or more doses of intravenous vitamin C 1500 mg for the treatment of sepsis and had at least two paired POC BG levels and laboratory venous BG levels measured within 1 hour of each other during vitamin C therapy. Measurements and Main Results: The performance of POC BG level measurement was compared with the reference method of laboratory BG level measurement. The concordance to minimum accuracy criteria for BG meters set forth by the International Organization for Standardization (ISO) 15197:2013, the measurement of agreement between POC BG level and laboratory BG level using the Bland‐Altman method, and the clinical accuracy through Parkes error grid analysis were assessed. A total of 16 paired POC and laboratory BG level measurements from the five patients were included. The accuracy of POC BG with laboratory BG level measurements during vitamin C administration according to ISO 15197:2013 criteria was 81.3%, which did not meet the minimum accuracy criteria of 95%. The Bland‐Altman analysis showed a mean difference between POC and laboratory BG levels of 8.9 mg/dl, and the Parkes error grid analysis showed that the differences between POC and laboratory BG level measurements would not have resulted in a change in clinical action. Conclusion: The accuracy and agreement of POC and laboratory BG level measurements in critically ill patients receiving vitamin C were consistent with previously published reports in critically ill patients not receiving vitamin C and did not demonstrate clinically significant interference due to vitamin C dosing for sepsis. [ABSTRACT FROM AUTHOR]

Provision of adequate sedation is a fundamental part of caring for critically ill patients. Propofol, dexmedetomidine, and benzodiazepines are the most commonly administered sedative medications for adult patients in the intensive care unit ( ICU). These agents are limited by adverse effects, need for a monitored environment for safe administration, and lack of universal effectiveness. Increased interest has recently been expressed about repurposing older pharmacologic agents for patient comfort in the ICU. Valproate, enteral clonidine, and phenobarbital are three agents with increasing evidence supporting their use. Potential benefits associated with their utilization are cost minimization and safe administration after transition out of the ICU. This literature review describes the historical context, pharmacologic characteristics, supportive data, and practical considerations associated with the administration of these agents for comfort in critically ill adult patients. [ABSTRACT FROM AUTHOR]

The article discusses the accurate recognition of delirium experienced by patients in the intensive care unit (ICU). It presents several reports on the use of a tool-based approach to diagnose delirium among critically ill patients. Medical personnel are warned about the negative effect of patients too sedated on delirium assessment rates. In addition, the article provides a study which examined the effect of intravenous haloperidol on the duration of delirium.

The authors discuss aspects of the American College of Critical Care Medicine guidelines for management of pain, agitation, and delirium (PAD). They highlight some of the 54 recommendations and observations from the PAD Task Force including the routine monitoring of pain and delirium in all adult intensive care unit (ICU) patients, and the use of preemptive analgesic therapy before clinical procedures. Moreover, the authors suggest reviewing the guidelines for the benefit of ICU patients.

Introduction: Alcohol withdrawal is common among intensive care unit (ICU) patients, but no current practice guidelines exist. We reviewed published manuscripts for prevalence, risk factors, screening tools, prophylactic and treatment strategies, and outcomes for alcohol withdrawal syndrome (AWS) and delirium tremens (DT) in the critically ill. Methods: The following databases: PubMed, MEDLINE, Embase, Cochrane Database of Systematic Reviews and Central Register of Controlled Trials, CINAHL, Scopus, Web of Knowledge, pain, anxiety and delirium (PAD) Guidelines REFWORKS, International Pharmaceutical Abstracts and references for published papers were searched. Publications with high or moderate Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Oxford levels of evidence were included. Results: Reported AWS rates range from <1 % in 'all ICU comers' to 60 % in highly selected alcohol-dependent ICU patients. Alcohol dependence and a history of withdrawal are significant risk factors for AWS occurrence. No screening tools for withdrawal have been validated in the ICU. The benefit of alcohol withdrawal prophylaxis is unproven, and proposed regimens appear equivalent. Early and aggressive titration of medication guided by symptoms is the only feature associated with improved treatment outcome. Conclusions: Treatment of AWS is associated with higher ICU complication rates and resource utilization. The optimal means of identification, prevention and treatment of AWS in order to establish evidence-based guidelines remain to be determined. [ABSTRACT FROM AUTHOR]

The article presents a study on the connection between the number of delirium days experienced by patients in intensive care units (ICUs) and the length of stay in the ICU, ventilation time, and mortality. The study involved 354 ICU patients enrolled in Safety and Efficacy of Dexmetomidine Compared with Midazolam (SEDCOM) trial. Results showed that the length of delirium was the strongest predictor for stay, ventilation time and mortality in lightly sedated and ventilated patients.

Objective: To compare available instruments for assessing delirium in critically ill adults that have undergone validity testing and provide clinicians with strategies to incorporate these instruments into clinical practice.Design: Medline (1966-September 2006) was searched using the key words: delirium, cognitive dysfunction, assessment, intensive care unit, and critical illness to identify assessment tools that have been used to evaluate delirium in critically ill adults. A special emphasis was placed on delirium assessment tools that have been properly validated. Data on how these tools have been adopted into clinical practice as well as strategies for clinicians to improve delirium assessment in the ICU are highlighted.Measurements and Results: Six delirium assessment instruments including the Cognitive Test for Delirium (CTD), abbreviated CTD, Confusion Assessment Method-ICU, Intensive Care Delirium Screening Checklist, NEECHAM scale, and the Delirium Detection Score were identified. While each of these scales have undergone validation in critically ill adults, substantial differences exist among the scales in terms of the quality and extent of the validation effort, the specific components of the delirium syndrome each address, their ability to identify hypoactive delirium, their use in patients with a compromised level of consciousness, and their ease of use.Conclusions: Incorporation of delirium assessment into clinical practice in the intensive care unit using a validated tool may improve patient care. Clinicians can adopt a number of different strategies to overcome the many barriers associated with routine delirium assessment in the ICU. [ABSTRACT FROM AUTHOR]

Purpose: Critically ill patients are occasionally resistant to, or become intolerant of, standard sedating agents. We describe our experience using phenobarbital (PB) as an alternative sedative in a select cohort of patients. Methods: Medical records of adult patients treated with PB for sedation were retrospectively reviewed. Patients receiving barbiturates for seizures, brain injury, or drug withdrawal protocols were excluded. Data are presented as mean ± standard deviation or median (range). Results: Seven patients were treated with PB after failing standard medications due to refractory agitation (five patients) or propylene glycol toxicity (two patients). Patients were 35 ± 10-years-old, six were female (86%), APACHE II was 16 ± 5, ICU stay was 16 (8 to 88) days, and all seven patients survived. Four patients were initially sedated with lorazepam (mean daily dose = 163 mg), two with propofol (mean dose = 51 mcg/kg/min), and one with both. All seven received fentanyl for analgesia. Patients were switched to PB on ICU day-6 (3 to 50) with 240 (60 to 490) mg given the first day in divided doses. Subsequent doses were titrated to desired response, typically Sedation Agitation Scale (SAS) 3. PB was continued for 6 (3 to 21) days. Quality of sedation appeared similar when assessed with average SAS of 3.5 pre vs 3.7 post, as well as, by the absence of both oversedation (SAS less 3) and medical device removal. Hemodynamic derangements were not noted, and four patients were extubated while receiving PB. Conclusions: PB provides adequate sedation and may be an alternative for patients intolerant or unresponsive to standard agents. [ABSTRACT FROM AUTHOR]

The bispectral index (BIS) is processed electroencephalographic technology used in concert with clinical evaluations to objectively evaluate a patient's level of consciousness and probability of recall. Although the BIS has been extensively studied in the operating room setting, differences in patient populations, goals of treatment, and the environments themselves necessitate the development of BIS data specific to the intensive care unit. Data have evolved over the last several years, but for many reasons, the results and conclusions have varied. Yet within the data are important consistencies that help define the usefulness of BIS in patients who cannot be evaluated with subjective assessment tools such as the Sedation-Agitation Scale or the Richmond Agitation-Sedation Scale. Some of these patients cannot be evaluated with such tools because they lack motor responsiveness due to therapeutic paralysis or because they are receiving deep sedation. Bispectral index scores that are higher than expected in clinically sedated patients can often be traced to electromyographic activity or to the possibility of inadequate sedation and analgesia. The BIS must not be regarded as the sole indicator of level of consciousness, but should be used as part of an integrated approach to the evaluation of carefully selected patients with critical illness. [ABSTRACT FROM AUTHOR]

We report a case of successful treatment of propylene glycol toxicity by discontinuation of propylene glycol administration and hemodialysis therapy. A critically ill woman receiving high dose intravenous lorazepam therapy is described. Although propylene glycol toxicity often resolves promptly after discontinuation of the causative parenteral source, renal or liver dysfunction may prolong the sequelae of propylene glycol infusion. Hemodialysis efficiently lowers propylene glycol serum concentrations in a manner analogous to extracorporeal therapy for other small molecular weight alcohol intoxications. Therefore, hemodialysis may be a useful component of therapy for critically ill patients exhibiting propylene glycol toxicity in the context of multiple organ dysfunction. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients. [ABSTRACT FROM AUTHOR]

The article evaluates the impact of individual manifestations of delirium on patient outcome in the U.S. In addition, it also describe the critically ill adults, and validate nurses' bedside item assessments from the Intensive Care Delirium Screening Checklist (ICDSC). It concludes that agitation was associated with a higher risk of mortality in nondelirious patients. Moreover, each of the eight ICDSC items is highly discriminating for the diagnosis of delirium.

The authors stress that clinicians have to avoid deep sedation at night for critically ill patients whenever possible. They cite other strategies that will help avoid delirium and coma and facilitate liberation from mechanical ventilation like use of linked spontaneous awakening and breathing trial strategies. They reference the study "Diurnal Sedative Changes During Intensive Care: Impact on Liberation From Mechanical Ventilation and Delirium" by C. W. Seymour and colleagues within the issue.

Objective: To describe and analyze the development and psychometric properties of subjective sedation scales developed for critically ill adult patients. Data Sources: PubMed, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, ISI Web of Science, and the International Pharmaceutical Abstracts. Study Selection: English-only publications through December 2012 with at least 30 patients older than 18 years, which included the key words of adult, critically ill, subjective sedation scale, sedation scale, validity, and reliability. Data Extraction: Two independent reviewers evaluated the psychometric properties using a standardized sedation scale psychometric scoring system. Data Synthesis: Among the 19,000+ citations extracted for the 2013 Society of Critical Care Medicine's Clinical Practice Guidelines for the Management of Pain, Agitation and Delirium and from December 2010 to 2012, 36 articles were identified compassing 11 sedation scales. The scale development process, psychometric properties, feasibility, and implementation of sedation scales were analyzed using a 0-20 scoring system. Two scales demonstrated scores indicating "very good" published psychometric properties: Richmond Agitation-Sedation Scale (19.5) and the Sedation-Agitation Scale (19). Scores with "moderate" properties include the Vancouver Interaction and Calmness Scale (1 4.3), Adaptation to the Intensive Care Environment (1 3.7), Ramsay Sedation Scale (1 3.2), Minnesota Sedation Assessment Tool (13), and the Nursing Instrument for the Communication of Sedation (1 2.8). Scales with "low" properties included the Motor Activity Assessment Scale (11 .5) and the Sedation Intensive Care Score (10.5). The New Sheffield Sedation Scale (8.5) and the Observer's Assessment of Alertness/Seda- tion Scale (3.7) demonstrated "very low" published properties. Conclusions: Based on the current literature, and using a prede- termined psychometric scoring system, the Richmond Agitation-Sedation Scale and the Sedation-Agitation Scale are the most valid and reliable subjective sedation scales for use in critically ill adult patients. [ABSTRACT FROM AUTHOR]

The article discusses the revision of the Clinical Practice Guidlines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" which was published in "Critical Care Medicine" in 2002. A task force of experts in guidance development for critically ill adult patients was assembled by the American College of Critical Care Medicine. It noted that these guidelines serve as a roadmap for developing patient-centered protocols for preventing pain in critically ill patients.

Five (13%) courses experienced both refractory hypokalemia during PB and rebound hyperkalemia following PB. Atrial fibrillation occurred during hypokalemia in 1 (3%) course during PB and ventricular tachycardia occurred during hypokalemia in 2 (5%) courses after PB. Confounders were common in those with hypokalemia during PB (mannitol 39%, hypothermia 67%) and those with hyperkalemia following PB (acute kidney injury 60%). [Extracted from the article]