Pharmacokinetics in Critically Ill Patients, What Changes?

BACKGROUND:The cellular immune system is of pivotal importance with regard to the response to severe infections. Monocytes/macrophages are considered key immune cells in infections and downregulation of the surface expression of monocytic human leukocyte antigen-DR (mHLA-DR) within the major histocompatibility complex class II reflects a state of immunosuppression, also referred to as injury-associated immunosuppression. As the role of immunosuppression in coronavirus disease 2019 (COVID-19) is currently unclear, we seek to explore the level of mHLA-DR expression in COVID-19 patients.METHODS:In a preliminary prospective monocentric observational study, 16 COVID-19–positive patients (75% male, median age: 68 [interquartile range 59–75]) requiring hospitalization were included. The median Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score in 9 intensive care unit (ICU) patients with acute respiratory failure was 30 (interquartile range 25–32). Standardized quantitative assessment of HLA-DR on monocytes (cluster of differentiation 14+ cells) was performed using calibrated flow cytometry at baseline (ICU/hospital admission) and at days 3 and 5 after ICU admission. Baseline data were compared to hospitalized noncritically ill COVID-19 patients.RESULTS:While normal mHLA-DR expression was observed in all hospitalized noncritically ill patients (n = 7), 89% (8 of 9) critically ill patients with COVID-19–induced acute respiratory failure showed signs of downregulation of mHLA-DR at ICU admission. mHLA-DR expression at admission was significantly lower in critically ill patients (median, [quartiles]: 9280 antibodies/cell [6114, 16,567]) as compared to the noncritically ill patients (30,900 antibodies/cell [26,777, 52,251]), with a median difference of 21,508 antibodies/cell (95% confidence interval [CI], 14,118–42,971), P = .002. Reduced mHLA-DR expression was observed to persist until day 5 after ICU admission.CONCLUSIONS:When compared to noncritically ill hospitalized COVID-19 patients, ICU patients with severe COVID-19 disease showed reduced mHLA-DR expression on circulating CD14+ monocytes at ICU admission, indicating a dysfunctional immune response. This immunosuppressive (monocytic) phenotype remained unchanged over the ensuing days after ICU admission. Strategies aiming for immunomodulation in this population of critically ill patients should be guided by an immune-monitoring program in an effort to determine who might benefit best from a given immunological intervention.

Medical intensive care unit (MICU) nurses often struggle to balance technological competence, task proficiency, and attention to the psychosocial needs of patients. They routinely are involved in negotiations to maintain or withdraw life-support. Knowledge is limited, however, on how nurses move from aggressively attempting to extend life to letting life end. The purpose of this qualitative research investigation was to explore nurses' experiences of moving from cure-oriented to comfort-oriented care in the MICU setting. The use of a descriptive qualitative research design with brief selective participant observation and focus group interviews was used to capture the nurses' experiences. The study took place in an eighteen-bed state-of-the-art MICU that was part of a 719-bed acute care hospital located in the northeastern United States. Nineteen female and five male nurses participated in the study. The analytic process followed the method described by Miles and Huberman (1994) that included data reduction, data display, and conclusion drawing. Demographic data, focus group transcripts, and observational field notes were reviewed independently by two group facilitators. The data were also presented to the research participants for review. Nurses did not describe a clear transition point moving from cure-oriented to comfort-oriented care. Several of the following factors influenced transitions in care: the patient's medical condition and illness trajectory, prognosis, response to medical interventions, length of time on the MICU, advanced directives, and degree of family consensus about treatment goals. Nurses reported that the age of the patient, the family's misunderstanding of the patient's illness, family discord, and shifting medical care decisions made providing patient care difficult. Developing consensus about the direction of medical therapy, exhausting treatment options, and patients' failing to respond to aggressive medical interventions helped nurses move toward comfort care. Nurses realized that patients might die and that there were fates worse than death. They acknowledged that witnessing a patient death was not similar to losing someone close or like a death in one's own family. Nurses utilized a variety of personal strategies to cope with transitions in patient care such as cognitive, affective, and behavioral strategies.

ObjectiveTo clarify variations of diagnosis and treatment in the emergency care of critically ill patients not infected with novel coronavirus (COVID-19) prior to and amidst the COVID-19 pandemic.MethodsA retrospective cohort study was conducted to compare and analyze the diagnosis and treatment data of critically ill patients with non-COVID-19 infection who were admitted to the emergency department of the Fourth Medical Center of Chinese PLA General Hospital from January 2019 to November 2022. The variations in emergency care of the pandemic were summarized, and the influence of the pandemic on emergency care was assessed.ResultsA total of 6634 critically ill patients with non-COVID-19 infection were included in this study. These patients were elderly, high incidence of chronic diseases, and extended emergency duration during the pandemic. Notably, the proportion of patients requiring intensive care was twofold higher compared to the period before the pandemic. Throughout the pandemic, patients experienced prolonged emergency durations, increased overall costs and daily expenses per patient. Further investigation revealed that elderly patients exhibited worse medical conditions, requiring lengthier emergency treatment and incurring escalated healthcare expenses. However, the presence of pre-existing chronic diseases did not appear to influence disease severity, nor extended emergency durations or heightened healthcare expenditures. Irrespective of the pandemic phase—be it short-term, medium-term, or long-term emergency care—greater healthcare spending was necessary.ConclusionThere was no difference in the disease spectrum of emergency critical ill patients with non-COVID-19 infection prior to and amidst the COVID-19 pandemic, nor the duration and expenditure in prior chronic illness patients. However, the disease severity and emergency duration have led to an increase in the total cost and economic intensity of emergency care for all patients during the epidemic. Especially, elderly patients required longer emergency duration, greater healthcare spending, and more inpatient medical resources than usual.

BackgroundSeverely ill patients are vulnerable to developing Acute Kidney Injury (AKI), with variable incidence, but limited data from LMICs. We evaluated the incidence, predictors, treatment, and outcomes of AKI among very ill adult patients at a public tertiary hospital in southwestern Uganda.MethodsThis prospective cohort study categorized patients who had a NEWS-2 above 5 as critically ill. We used the “Kidney Disease Improving Global Outcomes (KDIGO)” definition of AKI as a 0.3 mg/dl increase in serum creatinine within 48 hours. Participants were followed up until day 7 of admission, death or discharge, whichever occurred first. STATA version 13 was used for data analysis. Predictors of AKI were determined by logistic regression.ResultsOf 161 critically ill patients, the median age was 48 years (IQR: 31–65). The incidence of AKI was 70 (95% CI 55–90) per 1000 person days of observation. About, 39.1% (127) drugs used during hospitalization were deemed potentially nephrotoxic, and 60% (96) of participants were exposed to at least one nephrotoxic drug. Penicillins and loop diuretics were the most commonly used nephrotoxic drugs. Predictors of AKI included: previous hospitalization in the last 3 months (aOR 2.56, 95% CI: 1.08–6.06, P=0.032), admission to the surgical ward (aOR 4.32, 95% CI: 1.22–15.24, P=0.023), elevated baseline creatinine (>1.2 mg/dl) (aOR 2.44, 95% CI: 1.13–5.27, P=0.023) and elevated baseline WBC count (>12 × 109/µL) (aOR 2.57, 95% CI: 1.21–5.46, P=0.014). Most AKI patients were managed conservatively; 25% of patients with stage 3 received hemodialysis, and 25% of those with incident AKI died in the hospital.ConclusionWe found a high prevalence of AKI among critically ill patients (70 per 1000 person days). Previous hospitalization in the past 3 months, high baseline creatinine, high baseline WBC count and admission to the surgical ward were independently associated with AKI.

Efficacy and safety of therapeutic vs. prophylactic bemiparin in noncritically ill patients with COVID-19 pneumonia

The goal of this study was to compare pretransplant patient HRQOL, parent psychological functioning, and the impact of the patient's ongoing illness on the family between organ types (ie, kidney, liver, heart) and age-groups (ie, children, AYAs). The sample included 80 pediatric patients with end-stage organ disease who were evaluated for transplantation and their parents. Parents completed self- and proxy reports at patients' pretransplant evaluations. Results indicated that patients evaluated for heart transplants consistently had lower HRQOL and their parents had greater psychological distress compared to the kidney and liver groups. Within the heart group, parents and families of children (<12years old) experienced significantly more distress and impact of the patient's illness on the family compared to those of AYAs (≥12years old). Pediatric patients awaiting heart transplants, particularly younger children, and their parents and families may have greater psychosocial needs compared to patients awaiting kidney or liver transplants.

To characterize the limitation of care in routine geriatric practice in advance of and at the time of a patient's final episode of illness. A descriptive study performed by retrospective chart review. An outpatient geriatric practice affiliated with a community teaching hospital. Fifty-nine recipients of primary care who were community-dwelling and older than 65, died in the years 1988-1991, and were enrolled in the practice for at least 6 months prior to death. We recorded the type(s) of care patients (or, in the case of incompetence, their families) and their physicians chose to limit during the last episode of illness preceding death and during previous episodes of illness by examining those instances when therapy other than that considered "standard" was given. We also examined whether the presence of dementia, functional impairment, chronic disease, terminal illness, site of routine care (home vs hospital), and location of death were associated with the limitation of care. A choice to limit diagnostic tests or treatment was made by the patient or surrogate in 40% of the 59 patients during the 6 months before the patient's final episode of illness. Most frequently limited were diagnostic tests, surgery, and hospitalization for purposes other than surgery. Terminal illness and location of death were associated with the limitation of care, but dementia, functional impairment, chronic illness, and location of care were not. By comparison, 89% of the patients had limitation of care during the final episode of illness, and more aggressive therapies such as cardiopulmonary resuscitation and intubation constituted the majority of therapies withheld. In one geriatric practice, care is frequently limited before a patient's final illness in the course of routine practice. In contrast to recent discussion focusing on limitation of end-of-life interventions or interventions in the severely impaired, these results suggest that there are multiple points in the course of a community-dwelling elderly patient's illness at which choices about level of care can be made. Given this opportunity, a significant number of elderly patients of their surrogates will choose less intensive therapy.

Following the introduction of a carotid colour duplex Doppler service, a retrospective survey of the second 100 patients examined was undertaken to determine the accuracy of the examination compared with angiography and surgery, and to assess the clinical efficacy of the results with a review of the final diagnosis, how that diagnosis was achieved and whether the test had helped assess the patient's illness or altered the medical management and/or the outcome of the patient's illness. The results indicated the expected accuracy of over 94% and that the examination helped assess the patient's illness in 92%, altered the management plan in 40% and altered the outcome of the patient's illness in 14% where the disease prevalence was 16%.

Nirmatrelvir and ritonavir are two co-administered antiviral medications, marketed under the name Paxlovid in Canada, for the treatment of SARS-CoV-2 infection. Nirmatrelvir is an inhibitor of SARS-CoV-2 3CL-like protease that prevents polyprotein cleavage of proteins necessary for SARS-CoV-2 genome replication. Nirmatrelvir has been studied in combination with ritonavir, a medication that has no known activity against SARS-CoV-2 but slows the metabolism of nirmatrelvir by inhibiting hepatic enzymes, thus “boosting” concentrations of nirmatrelvir. Nirmatrelvir/ritonavir is currently approved in Canada for the treatment of mild COVID-19 (termed “mild to moderate” with Health Canada’s terminology) in those who are at high risk for progression to severe or critical COVID-19 illness. It is not approved for the treatment of patients requiring hospitalization due to COVID-19, nor for pre- or post-exposure prophylaxis for the prevention of SARS-CoV-2 infection. As of the date of publication of this Science Brief, there is one peer-reviewed publication comparing nirmatrelvir/ritonavir against placebo. Nirmatrelvir/ritonavir reduces the incidence of hospitalization and/or death in patients with mild COVID-19 with risk factors for progression to moderate or critical illness, with fewer treatment-emergent serious adverse events relative to placebo. The panel noted a marginal benefit in individuals at low risk of hospitalization, and the high certainty of harm with nirmatrelvir/ritonavir if known drug-drug interactions are not mitigated. Critically Ill Patients (On High-Flow Oxygen, Mechanical Ventilation, or Extracorporeal Membrane Oxygenation (ECMO)) Nirmatrelvir/ritonavir is not recommended for critically ill patients with COVID-19. Moderately Ill Patients (On Low-Flow Oxygen) Nirmatrelvir/ritonavir is not recommended for moderately ill patients with COVID-19. Mildly Ill Patients (Not Requiring Supplemental Oxygen) Nirmatrelvir/ritonavir is recommended at a dose of 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three tablets taken together orally twice daily for five days. Patients must be at higher risk of severe disease from COVID-19 and present within five days of symptom onset. Risk factors for progression to moderate or critical COVID-19 are outlined in “Methods used for this Science Brief” below, and include immunocompromised individuals, and individuals whose combination of age, vaccination history, and risk factors put them at increased risk of progression to severe disease. Other treatment options that may be available to these higher risk patients include sotrovimab, remdesivir, fluvoxamine, and budesonide. Clinicians should consider patient-specific factors including (but not limited to) drug-drug interactions, renal function, duration of COVID-19 symptoms, ability to administer intravenous versus oral drugs, strength of evidence, situational context, and drug supply in decision-making regarding choice of therapy (see Therapeutic Management of Adult Patients with COVID-19 summary for additional details). If eligible patients with mild COVID-19 who began treatment with nirmatrelvir/ritonavir progress to moderate COVID-19 during their treatment course, they may complete their treatment course at the discretion of the treating physician. Implementation Considerations It is recommended that oral antiviral therapy be administered to non-hospitalized individuals across Ontario using a hybrid network that includes, but is not limited to, mobile integrated healthcare services, community paramedicine, virtual/remote assessment, and outpatient clinics. Special Populations Pharmacist consultation is important to mitigate any significant drug-drug interactions (including natural products). Nirmatrelvir/ritonavir is contraindicated in patients taking certain medications that have the potential for serious or life-threatening reactions at high concentrations and are highly dependent on CYP3A4-mediated metabolism; and in patients taking certain medications that are CYP3A-inducing, as these may significantly decrease concentrations of nirmatrelvir/ritonavir, decreasing its efficacy as a COVID-19 treatment (see Tables 1-4 in the “Considerations” section below, and the guidance document “Nirmatrelvir/ritonavir (Paxlovid): What prescribers and pharmacists need to know”). For complex interactions, consultation with a pharmacist experienced in managing ritonavir-related interactions may be helpful. In patients with moderate renal impairment (eGFR ≥30 to

As Accessible as a Book on a Library Shelf: The Imperative of Routine Simulation in Modern Health Care

Compromised Autonomy and the Seriously Ill Patient

There are fewtools to help physiciansconduct serious illnessconversations during a health crisis, where there is a high probability of imminent death. The Serious Illness Conversation Guide (SICG) offers physicians a framework to lead conversations with seriously ill patients in a stable setting and may be adaptable to crisis communication. To identify the communication skills and strategies used by expert clinicians in crisis situations and to determine if the SICG can be adapted for use in crisis situations. We performed semi-structured interviews of physicians with experience in crisis communication and analyzed the transcripts using thematic analysis. Based on our results, we developed a preliminary adaptation of the SICG for crisis communication. We interviewed general internists (n = 8), intensive care (n = 3), and emergency medicine physicians (n = 7) who worked at The Ottawa Hospital, a tertiary care hospital in Ottawa, Canada. Physicians described several challenges to conducting serious illness conversations in crisis, including time constraints, uncertaintyin prognosis, limited access to the patient's medical history, lack of an established therapeutic relationship, and a potentially high symptom burden. They outlined strategies to support communication in these settings, such as rapidly establishing trust, being transparent about uncertainty and allowing space for emotional expression. While all physicians agreed the SICG was adaptable to crisis settings, they noted the need to modify some of the language to better reflect the high-acuity setting. Elements of crisis communication absent from the SICG included gathering information on the medical context and prior wishes, assessing capacity, establishing the substitute decision-maker, involving family, and understanding the patient's pre-hospital quality of life and illness experience. We identified key skills and strategies for crisis communication. The SICG is relevant and adaptable for crisis communication. Future studies should test the adapted guide amongst patients and their caregivers.

Pressure ulcers are preventable events. Critically ill patients are particularly vulnerable. The Braden scale has been used to identify hospitalized patients at high risk for the development of pressure ulcers; however, this predictive tool has not been adequately validated for critically ill patients. We aimed to validate and improve the Braden scale for critically ill patients by adding clinical variables to the original scale. We conducted a cohort study in 12 intensive care units (ICUs) within a network of hospitals in Brazil during 2013. We excluded patients who stayed less than 48 hours, patients with one or more pressure ulcers at admission, and those who developed a pressure ulcer within the first 48 hours. We evaluated the Braden scale and clinical variables through a competing risk analysis. Discrimination and calibration were evaluated using the Concordance index (C-index) and a calibration plot, respectively. We used bootstrapping to assess internal validation. Our primary outcome was incident pressure ulcer within 30 days of ICU admission. We analyzed 9,605 patients and observed 157 pressure ulcers (rate of 3.33 pressure ulcers/1,000 patient-days). The majority of pressure ulcers were detected at stage I or II (28.7 and 66.2%, respectively). The Braden scale had good discrimination (C-index, 0.753; 95% confidence interval, 0.712-0.795), although its performance decreased for the most severely ill patients. We derived a modified predictive tool by adding eight clinical variables to the Braden scale: age, sex, diabetes mellitus, hematological malignancy, peripheral artery disease, hypotension at ICU admission, and need for mechanical ventilation or renal replacement therapy in the first 24 hours after ICU admission. The derived score had better discrimination and calibration than the original Braden scale. The best score cutoff was at least 6 points, with a sensitivity of 87% and a specificity of 71%. The original Braden scale measured at ICU admission is a valuable tool for pressure ulcer prediction, although it is not accurate for severely ill patients. To overcome the limitations of the original scale, we derived a modified score with better performance, which may identify high-risk ICU patients and support target interventions. External validation of the proposed clinical prediction score is needed.

Effective communication between clinicians and seriously ill patients and their families about a patient's goals of care is essential to patient-centered, goal-concordant, end-of-life care. Effective goals-of-care communication between clinicians and patients is associated with improved patient and family outcomes, increased clinician satisfaction, and decreased health care costs. Unfortunately, clinicians often face barriers in goals-of-care communication and collaboration, including a lack of education, time constraints, and no standardized protocols. Without clear goals-of-care communication, patients may not be able to provide guidance to clinicians about their end-of-life preferences. The purpose of this integrative review was to examine the efficacy of goals-of-care communication interventions between patients, families, and clinicians in randomized controlled trials published between 2009 and 2018. Twenty-three studies met the inclusion criteria with an overall sample (N = 6376) of patients, family members, and clinicians. Results revealed of the 6 different intervention modes, patient decision aids and patient-clinician communication consistently increased comprehension and communication. Twelve of the studies had nurses facilitate or support the communication intervention. Because nurses are a critical, trusted nexus for communication about end-of-life care, focusing on nurse interventions may significantly improve clinical outcomes and the patient experience.

Care of the Critically Ill Surgical Patient