The cholinergic anti-inflammatory pathway (CAP) refers to the anti-inflammatory effects mediated by the parasympathetic nervous system. Existence of this pathway was first demonstrated when acetylcholinesterase inhibitors showed benefits in animal models of sepsis. CAP functions via the vagus nerve. The systemic anti-inflammatory effects of CAP converges on the α7 nicotinic acetylcholine receptor on splenic macrophages, leading to suppression of pro-inflammatory cytokines and simultaneous stimulation of anti-inflammatory cytokines, including interleukin 10. CAP offers a novel mechanism to mitigate inflammation. Electrical vagal nerve stimulation has shown benefits in patients suffering from rheumatoid arthritis. Direct agonists like nicotine and GTS-1 have also demonstrated anti-inflammatory properties in models of sepsis and acute respiratory distress syndrome, as have acetylcholinesterase inhibitors like Galantamine and Physostigmine. Experience with coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome indicates that immunomodulators have a protective role in patient outcomes. Dexamethasone is the only medication currently in use that has shown to improve clinical outcomes. This is likely due to the suppression of what is referred to as a cytokine storm, which is implicated in the lethality of viral pneumonia. Nicotine transdermal patch activates CAP and harvests its anti-inflammatory potential by means of an easily administered depot delivery mechanism. It could prove to be a promising, safe and inexpensive additional tool in the currently limited armamentarium at our disposal for management of COVID-19 induced acute hypoxic respiratory failure.
Mortality is a well-established patient-important outcome in critical care studies. In contrast, morbidity is less uniformly reported (given the myriad of critical care illnesses and complications of each) but may have a common end-impact on a patient's functional capacity and health-related quality-of-life (HRQoL). Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences. Hence, as mortality decreases within critical care, it becomes increasingly important to measure intensive care unit (ICU) survivor HRQoL. HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0 (representing death) and 1 (representing full health). They can be combined with survival to calculate quality-adjusted life-years (QALY), which are one of the most widely used methods of combining morbidity and mortality into a composite outcome. Although QALYs have been use for health-technology assessment decision-making, an emerging and novel role would be to inform clinical decision-making for patients, families and healthcare providers about what expected HRQoL may be during and after ICU care. Critical care randomized control trials (RCTs) have not routinely measured or reported HRQoL (until more recently), likely due to incapacity of some patients to participate in patient-reported outcome measures. Further differences in HRQoL measurement tools can lead to non-comparable values. To this end, we propose the validation of a gold-standard HRQoL tool in critical care, specifically the EQ-5D-5L. Both combined health-utility and mortality (disaggregated) and QALYs (aggregated) can be reported, with disaggregation allowing for determination of which components are the main drivers of the QALY outcome. Increased use of HRQoL, health-utility, and QALYs in critical care RCTs has the potential to: (1) Increase the likelihood of finding important effects if they exist; (2) improve research efficiency; and (3) help inform optimal management of critically ill patients allowing for decision-making about their HRQoL, in additional to traditional health-technology assessments.
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies.
Aim: To describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of hyperinflammation and abnormal immune responses to disease progression together with a complete narrative review of the different immunoadjuvant treatments used so far in COVID-19 and their indication in severe and life-threatening subsets.
Methods: A comprehensive literature search was developed. Authors reviewed the selected manuscripts following the PRISMA recommendations for systematic review and meta-analysis documents and selected the most appropriate. Finally, a recommendation of the use of each treatment was established based on the level of evidence of the articles and documents reviewed. This recommendation was made based on the consensus of all the authors.
Results: A brief rationale on the SARS-CoV-2 pathogenesis, immune response, and inflammation was developed. The usefulness of 10 different families of treatments related to inflammation and immunopathogenesis of COVID-19 was reviewed and discussed. Finally, based on the level of scientific evidence, a recommendation was established for each of them.
Conclusion: Although several promising therapies exist, only the use of corticosteroids and tocilizumab (or sarilumab in absence of this) have demonstrated evidence enough to recommend its use in critically ill patients with COVID-19. Endotypes including both, clinical and biological characteristics can constitute specific targets for better select certain therapies based on an individualized approach to treatment.
Background: The association between hospitalization for human respiratory syncytial virus (HRSV) bronchiolitis in early childhood and subsequent asthma is well established. The long-term prognosis for non-bronchiolitis lower respiratory tract infections (LRTI) caused by viruses different from HRSV and rhinovirus, on the other hand, has received less interest.
Aim: To investigate the relationship between infant LRTI and later asthma and examine the influence of confounding factors.
Methods: The PubMed and Global Index Medicus bibliographic databases were used to search for articles published up to October 2021 for this systematic review. We included cohort studies comparing the incidence of asthma between patients with and without LRTI at ≤ 2 years regardless of the virus responsible. The meta-analysis was performed using the random effects model. Sources of heterogeneity were assessed by stratified analyses.
Results: This review included 15 articles (18 unique studies) that met the inclusion criteria. LRTIs at ≤ 2 years were associated with an increased risk of subsequent asthma up to 20 years [odds ratio (OR) = 5.0, 95%CI: 3.3-7.5], with doctor-diagnosed asthma (OR = 5.3, 95%CI: 3.3-8.6), current asthma (OR = 5.4, 95%CI: 2.7-10.6), and current medication for asthma (OR = 1.2, 95%CI: 0.7-3.9). Our overall estimates were not affected by publication bias (P = 0.671), but there was significant heterogeneity [I 2 = 58.8% (30.6-75.5)]. Compared to studies with hospitalized controls without LRTI, those with ambulatory controls had a significantly higher strength of association between LRTIs and subsequent asthma. The strength of the association between LRTIs and later asthma varied significantly by country and age at the time of the interview. The sensitivity analyses including only studies with similar proportions of confounding factors (gender, age at LRTI development, age at interview, gestational age, birth weight, weight, height, smoking exposure, crowding, family history of atopy, and family history of asthma) between cases and controls did not alter the overall estimates.
Conclusion: Regardless of the causative virus and confounding factors, viral LRTIs in children < 2 years are associated with an increased risk of developing a subsequent asthma. Parents and pediatricians should be informed of this risk.
Hyperglycemia is commonly associated with adverse outcomes especially in patients requiring intensive care unit stay. Data from the corona virus disease 2019 (COVID-19) pandemic indicates that individuals with diabetes appear to be at similar risk for COVID-19 infection to those without diabetes but are more likely to experience increased morbidity and mortality. The proposed hypothesis for hyperglycemia in COVID-19 include insulin resistance, critical illness hyperglycemia (stress- induced hyperglycemia) secondary to high levels of hormones like cortisol and catecholamines that counteract insulin action, acute cytokine storm and pancreatic cell dysfunction. Diabetic patients are more likely to have severe hyperglycemic complications including diabetic ketoacidosis and hyperosmolar hyperglycemic state. Management of hyperglycemia in COVID-19 is often complicated by use of steroids, prolonged total parenteral or enteral nutrition, frequent acute hyperglycemic events, and restrictions with fluid management due to acute respiratory distress syndrome. While managing hyperglycemia special attention should be paid to mode of insulin delivery, frequency of glucose monitoring based on patient and caregiver safety thereby minimizing exposure and conserving personal protective equipment. In this article we describe the pathophysiology of hyperglycemia, challenges encountered in managing hyperglycemia, and review some potential solutions to address them.
Background: Patients leaving the intensive care unit (ICU) often experience gaps in care due to deficiencies in discharge communication, leaving them vulnerable to increased stress, adverse events, readmission to ICU, and death. To facilitate discharge communication, written summaries have been implemented to provide patients and their families with information on medications, activity and diet restrictions, follow-up appointments, symptoms to expect, and who to call if there are questions. While written discharge summaries for patients and their families are utilized frequently in surgical, rehabilitation, and pediatric settings, few have been utilized in ICU settings.
Aim: To develop an ICU specific patient-oriented discharge summary tool (PODS-ICU), and pilot test the tool to determine acceptability and feasibility.
Methods: Patient-partners (i.e., individuals with lived experience as an ICU patient or family member of an ICU patient), ICU clinicians (i.e., physicians, nurses), and researchers met to discuss ICU patients' specific informational needs and design the PODS-ICU through several cycles of discussion and iterative revisions. Research team nurses piloted the PODS-ICU with patient and family participants in two ICUs in Calgary, Canada. Follow-up surveys on the PODS-ICU and its impact on discharge were administered to patients, family participants, and ICU nurses.
Results: Most participants felt that their discharge from the ICU was good or better (n = 13; 87.0%), and some (n = 9; 60.0%) participants reported a good understanding of why the patient was in ICU. Most participants (n = 12; 80.0%) reported that they understood ICU events and impacts on the patient's health. While many patients and family participants indicated the PODS-ICU was informative and useful, ICU nurses reported that the PODS-ICU was "not reasonable" in their daily clinical workflow due to "time constraint".
Conclusion: The PODS-ICU tool provides patients and their families with essential information as they discharge from the ICU. This tool has the potential to engage and empower patients and their families in ensuring continuity of care beyond ICU discharge. However, the PODS-ICU requires pairing with earlier discharge practices and integration with electronic clinical information systems to fit better into the clinical workflow for ICU nurses. Further refinement and testing of the PODS-ICU tool in diverse critical care settings is needed to better assess its feasibility and its effects on patient health outcomes.
Recent research has demonstrated that critically ill patients with coronavirus disease 2019 (COVID-19) show significant immune system dysregulation. Due to that, some nutrients that influence immunomodulation have been suggested as a form of treatment against the infection. This review collected the information on the impact of vitamins on the prognosis of COVID-19, with the intention of facilitating treatment and prevention of the disease risk status in patients. The collected information was obtained using the PubMed electronic database by searching for articles that relate COVID-19 and the mechanisms/effects of the nutrients: Proteins, glucose, lipids, vitamin B12, vitamin D, calcium, iron, copper, zinc, and magnesium, including prospective, retrospective, and support articles. The findings reveal an optimal response related mainly to omega-3, eicosapentaenoic acid, docosahexaenoic acid, calcium, and iron that might represent benefits in the treatment of critically ill patients. However, nutrient supplementation should be done with caution due to the limited availability of randomized controlled studies.
Background: Coronavirus disease 2019 (COVID-19) can be associated with life-threatening organ dysfunction due to septic shock, frequently requiring intensive care unit (ICU) admission, respiratory and vasopressor support. Therefore, clear clinical criteria are pivotal for early recognition of patients more likely to need prompt organ support. Although most patients with severe COVID-19 meet the Sepsis-3.0 criteria for septic shock, it has been increasingly recognized that hyperlactatemia is frequently absent, possibly leading to an underestimation of illness severity and mortality risk.
Aim: To identify the proportion of severe COVID-19 patients with vasopressor support requirements, with and without hyperlactatemia, and describe their clinical outcomes and mortality.
Methods: We performed a single-center prospective cohort study. All adult patients admitted to the ICU with COVID-19 were included in the analysis and were further divided into three groups: Sepsis group, without both criteria; Vasoplegic Shock group, with persistent hypotension and vasopressor support without hyperlactatemia; and Septic Shock 3.0 group, with both criteria. COVID-19 was diagnosed using clinical and radiologic criteria with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR test.
Results: 118 patients (mean age 63 years, 87% males) were included in the analysis (n = 51 Sepsis group, n = 26 Vasoplegic Shock group, and n = 41 Septic Shock 3.0 group). SOFA score at ICU admission and ICU length of stay were different between the groups (P < 0.001). Mortality was significantly higher in the Vasoplegic Shock and Septic Shock 3.0 groups when compared with the Sepsis group (P < 0.001) without a significant difference between the former two groups (P = 0.713). The log rank tests of Kaplan-Meier survival curves were also different (P = 0.007). Ventilator-free days and vasopressor-free days were different between the Sepsis vs Vasoplegic Shock and Septic Shock 3.0 groups (both P < 0.001), and similar in the last two groups (P = 0.128 and P = 0.133, respectively). Logistic regression identified the maximum dose of vasopressor therapy used (AOR 1.046; 95%CI: 1.012-1.082, P = 0.008) and serum lactate level (AOR 1.542; 95%CI: 1.055-2.255, P = 0.02) as the major explanatory variables of mortality rates (R 2 0.79).
Conclusion: In severe COVID-19 patients, the Sepsis 3.0 criteria of septic shock may exclude approximately one third of patients with a similarly high risk of a poor outcome and mortality rate, which should be equally addressed.
Cough is a common respiratory complaint driving patients to seek medical advice. Besides being a fundamental respiratory sign, it is also a crucial neurological sign. There are three main types of coughs: Reflex cough (type I), voluntary cough (type II), and evoked cough (type III). Cough is a reflex predominantly mediated by control centers in the respiratory areas of the brainstem, modulated by the cerebral cortex. Cough reflex sensitivity could be increased in many neurological disorders such as brainstem space-occupying lesions, medullary lesions secondary to Chiari type I malformations, tics disorders such as Tourette's syndrome, somatic cough, cerebellar neurodegenerative diseases, and chronic vagal neuropathy due to allergic and non-allergic conditions. Meanwhile, cough sensitivity decreases in multiple sclerosis, brain hypoxia, cerebral hemispheric stroke with a brainstem shock, Parkinson's disease, dementia due to Lewy body disease, amyotrophic lateral sclerosis, and peripheral neuropathy as diabetic neuropathy, hereditary sensory and autonomic neuropathy type IV, vitamin B12, and folate deficiency. Arnold's nerve ear-cough reflex, syncopal cough, cough headache, opioids-associated cough, and cough-anal reflex are signs that could help diagnose underlying neurological conditions. Cough reflex testing is a quick, easy, and cheap test performed during the cranial nerve examination. In this article, we reviewed the role of cough in various neurological disorders that increase or decrease cough sensitivity.
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