Serotonin syndrome controversies:A need for consensus

Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.

Effects of nutrients on immunomodulation in patients with severe COVID-19:Current knowledge

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.

Implementation of a nurse-led protocol for early extubation after cardiac surgery: A pilot study

BACKGROUND Protocols for nurse-led extubation are as safe as a physician-guided weaning in general intensive care unit(ICU).Early extubation is a cornerstone of fast-track cardiac surgery,and it has been mainly implemented in post-anaesthesia care units.Introducing a nurse-led extubation protocol may lead to reduced extubation time.AIM To investigate results of the implementation of a nurse-led protocol for early extubation after elective cardiac surgery,aiming at higher extubation rates by the third postoperative hour.METHODS A single centre prospective study in an 18-bed,consultant-led Cardiothoracic ICU,with a 1:1 nurse-to-patient ratio.During a 3-wk period,the protocol was implemented with:(1)Structured teaching sessions at nurse handover and at bed-space(all staff received teaching,over 90%were exposed at least twice;(2)Email;and(3)Laminated sheets at bed-space.We compared“standard practice”and“intervention”periods before and after the protocol implementation,measuring extubation rates at several time-points from the third until the 24th postoperative hour.RESULTS Of 122 cardiac surgery patients admitted to ICU,13 were excluded as early weaning was considered unsafe.Therefore,109 patients were included,54 in the standard and 55 in the intervention period.Types of surgical interventions and baseline left ventricular function were similar between groups.From the third to the 12th post-operative hour,the intervention group displayed a higher proportion of patients extubated compared to the standard group.However,results were significant only at the sixth hour(58%vs 37%,P=0.04),and not different at the third hour(13%vs 6%,P=0.33).From the 12th post-operative hour time-point onward,extubation rates became almost identical between groups(83%in standard vs 83%in intervention period).CONCLUSION The implementation of a nurse-led protocol for early extubation after cardiac surgery in ICU may gradually lead to higher rates of early extubation.

Treatment and prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy

Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding complications such as gastrointestinal bleeding, which is one of the most common life-threatening complications. Early endoscopy is recommended for most patients with acute upper gastrointestinal bleeding. After successful endoscopic hemostasis, immediate resumption of antiplatelet therapy with proton-pump inhibitors(PPIs) is recommended to prevent further ischemic events. PPI prophylaxis during antiplatelet therapy reduces the risk of upper gastrointestinal bleeding. The potential negative metabolic interaction between PPIs and clopidogrel is still unclear.

Tumor lysis syndrome: A clinical review

Tumor lysis syndrome is an oncometabolic emergency resulting from rapid cell death. Tumor lysis syndrome can occur as a consequence of tumor targeted therapy or spontaneously. Clinicians should stratify every hospitalized cancer patient and especially those receiving chemotherapy for the risk of tumor lysis syndrome. Several aspects of prevention include adequate hydration, use of uric acid lowering therapies, use of phosphate binders and minimization of potassium intake. Patients at high risk for the development of tumor lysis syndrome should be monitored in the intensive care unit. Established tumor lysis syndrome should be treated in the intensive care unit by aggressive hydration, possible use of loop diuretics, possible use of phosphate binders,use of uric acid lowering agents and dialysis in refractory cases.

Extracorporeal membrane oxygenation for pediatric respiratory failure: History, development and current status

Extracorporeal membrane oxygenation(ECMO) is currently used to support patients of all ages with acute severe respiratory failure non-responsive to conventional treatments, and although initial use was almost exclusively in neonates, use for this age group is decreasing while use in older children remains stable(300-500 cases annually) and support for adults is increasing. Recent advances in technology include: refinement of double lumen veno-venous(VV) cannulas to support a large range of patient size, pumps with lower prime volumes, more efficient oxygenators, changes in circuit configuration to decrease turbulent flow and hemolysis. Veno-arterial(VA) mode of support remains the predominant type used; however, VV support has lower risk of central nervous injury and mortality. Key to successful survival is implementation of ECMO before irreversible organ injury develops, unless support with ECMO is used as a bridge to transplant. Among pediatric patients treated with ECMO mortality varies by pulmonary diagnosis, underlying condition, other nonpulmonary organ dysfunction as well as patient age, but has remained relatively unchanged overall(43%)over the past several decades. Additional risk factors associated with death include prolonged use of mechanical ventilation(> 2 wk) prior to ECMO, use of VA ECMO, older patient age, prolonged ECMO support as well as complications during ECMO. Medical evidence regarding daily patient management specifically related to ECMO is scant, it usually mirrors care recommended for similar patients treated without ECMO. Linkage of the Extracorporeal Life Support Organization dataset with other databases and collaborative research networks will be required to address this knowledge deficit as most centers treat only a few pediatric respiratory failure patients each year.

Point of care venous Doppler ultrasound: Exploring the missing piece of bedside hemodynamic assessment

Accurate assessment of the hemodynamic status is vital for appropriate management of patients with critical illness.As such,there has been a constant quest for reliable and non-invasive bedside tools to assess and monitor circulatory status in order to ensure end-organ perfusion.In the recent past,point of care ultrasonography(POCUS)has emerged as a valuable adjunct to physical examination in various specialties,which basically is a clinician-performed bedside ultrasound to answer focused questions.POCUS allows visualization of the internal anatomy and flow dynamics in real time,guiding apt interventions.While both arterial(forward flow)and venous(organ outflow or afterload)limbs of hemodynamic circuit are important for tissue perfusion,the venous side remains relatively under-explored.With recent data underscoring the deleterious consequences of iatrogenic volume overload,objective evaluation of venous congestion is gaining attention.Bedside Doppler ultrasound serves this purpose and aids in diagnosing and monitoring the congestion/venous blood flow pattern.In this article,we summarize the rationale for integrating this technology into routine care of patients with volume-related disorders,discuss the normal and abnormal waveforms,limitations,and future directions.

Anticoagulation with direct thrombin inhibitors during extracorporeal membrane oxygenation

Use of extracorporeal membrane oxygenation to support patients with critical cardiorespiratory illness is increasing.Systemic anticoagulation is an essential element in the care of extracorporeal membrane oxygenation patients.While unfractionated heparin is the most commonly used agent,unfractionated heparin is associated with several unique complications that can be catastrophic in critically ill patients,including heparin-induced thrombocytopenia and acquired antithrombin deficiency.These complications can result in thrombotic events and subtherapeutic anticoagulation.Direct thrombin inhibitors(DTIs)are emerging as alternative anticoagulants in patients supported by extracorporeal membrane oxygenation.Increasing evidence supports DTIs use as safe and effective in extracorporeal membrane oxygenation patients with and without heparininduced thrombocytopenia.This review outlines the pharmacology,dosing strategies and available protocols,monitoring parameters,and special use considerations for all available DTIs in extracorporeal membrane oxygenation patients.The advantages and disadvantages of DTIs in extracorporeal membrane oxygenation relative to unfractionated heparin will be described.

Therapeutic temperature modulation is associated with pulmonary complications in patients with severe traumatic brain injury

AIM: To examine complications associated with the use of therapeutic temperature modulation(mild hypothermia and normothermia) in patients with severe traumatic brain injury(TBI). METHODS: One hundred and fourteen charts were reviewed. Inclusion criteria were: severe TBI with Glasgow Coma Scale(GCS) < 9, intensive care unit(ICU) stay > 24 h and non-penetrating TBI. Patients were divided into two cohorts: the treatment group received therapeutic temperature modulation(TTM) with continuous surface cooling and indwelling bladder temperature probes. The control group received standard treatment with intermittent acetaminophen for fever. Information regarding complications during the time in the ICU was collected as follows: Pneumonia was identified using a combination of clinical and laboratory data. Pulmonary embolism, pneumothorax and deep venous thrombosis were identified based onimaging results. Cardiac arrhythmias and renal failure were extracted from the clinical documentation. acute respiratory distress syndrome and acute lung injury were determined based on chest imaging and arterial blood gas results. A logistic regression was conducted to predict hospital mortality and a multiple regression was used to assess number and type of clinical complications. RESULTS: One hundred and fourteen patients were included in the analysis(mean age = 41.4, SD = 19.1, 93 males), admitted to the Jackson Memorial Hospital Neuroscience ICU and Ryder Trauma Center(mean GCS = 4.67, range 3-9), were identified and included in the analysis. Method of injury included motor vehicle accident(n = 29), motor cycle crash(n = 220), blunt head trauma(n = 212), fall(n = 229), pedestrian hit by car(n = 216), and gunshot wound to the head(n = 27). Ethnicity was primarily Caucasian(n = 260), as well as Hispanic(n = 227) and African American(n = 223); four patients had unknown ethnicity. Patients received either TTM(43) or standard therapy(71). Within the TTM group eight patients were treated with normothermia after TBI and 35 patients were treated with hypothermia. A logistic regression predicting in hospital mortality with age, GCS, and TM demonstrated that GCS(Beta = 0.572, P < 0.01) and age(Beta =-0.029) but not temperature modulation(Beta = 0.797, ns) were significant predictors of in-hospital mortality [χ2(3) = 22.27, P < 0.01] A multiple regression predicting number of complications demonstrated that receiving TTM was the main contributor and was associated with a higher number of pulmonary complications(t =-3.425, P = 0.001). CONCLUSION: Exposure to TTM is associated with an increase in pulmonary complications. These findings support more attention to these complications in studies of TTM in TBI patients.

Approaches to neuroprotection in pediatric neurocritical care

Acute neurologic injuries represent a common cause of morbidity and mortality in children presenting to the pediatric intensive care unit.After primary neurologic insults,there may be cerebral brain tissue that remains at risk of secondary insults,which can lead to worsening neurologic injury and unfavorable outcomes.A fundamental goal of pediatric neurocritical care is to mitigate the impact of secondary neurologic injury and improve neurologic outcomes for critically ill children.This review describes the physiologic framework by which strategies in pediatric neurocritical care are designed to reduce the impact of secondary brain injury and improve functional outcomes.Here,we present current and emerging strategies for optimizing neuroprotective strategies in critically ill children.

Antithrombin in the treatment of burn trauma

Antithrombin(AT) is a natural anticoagulant with antiinflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT maydecrease blood loss during eschar excision, reducing blood transfusion requirements. There are no human randomized, placebo-controlled studies, which have tested the true benefit of this agent in these conditions. Two main forms of AT are either plasma-derived AT(ph AT) and recombinant AT(rh AT). Major ovine studies in burn and smoke inhalation injury have utilized rh AT. There have been no studies which have either translated the basic rh AT research in burn trauma, or determined the tolerance and pharmacokinetics of rh AT concentrate infusions in burn patients. Advantages of rh AT infusions are no risk of blood borne diseases and lower cost. However, the majority of human burn patient studies have been conducted utilizing ph AT. Recent Japanese clinical trials have started using ph AT in abdominal sepsis successfully. This review examines the properties of both ph AT and rh AT, and analyzes studies in which they have been utilized. We believe that it is time to embark on a randomized placebo-controlled multi-center trial to establish the role of AT in both civilian and military patients with burn trauma.

Optimizing the value of measuring inferior vena cava diameter in shocked patients

Point-of-care ultrasound has been increasingly used in evaluating shocked patients including the measurement of inferior vena cava(IVC) diameter. Operators should standardize their technique in scanning IVC. Relativechanges are more important than absolute numbers. We advise using the longitudinal view(B mode) to evaluate the gross collapsibility, and the M mode to measure the IVC diameter. Combining the collapsibility and diameter size will increase the value of IVC measurement. This approach has been very useful in the resuscitation of shocked patients, monitoring their fluid demands, and predicting recurrence of shock. Pitfalls in measuring IVC diameter include increased intra-thoracic pressure by mechanical ventilation or increased right atrial pressure by pulmonary embolism or heart failure. The IVC diameter is not useful in cases of increased intra-abdominal pressure(abdominal compartment syndrome) or direct pressure on the IVC. The IVC diameter should be combined with focused echocardiography and correlated with the clinical picture as a whole to be useful.

Diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients:A mini review for clinicians

Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease.In addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug reactions.To help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.

Predicting the risk of mortality in children with dengue-induced hepatitis admitted to the paediatric intensive care unit

BACKGROUND Dengue-associated acute liver failure(PALF)accounts for a high mortality rate in children admitted to the pediatric intensive care unit(PICU).To date,there is a lack of data on clinical algorithms for estimating the risk of mortality in pediatric patients with dengue-induced severe hepatitis(DISH).AIM To determine the prevalence of PALF and identify the predictors of mortality among patients with DISH.METHODS This single-institution retrospective study was performed at a tertiary pediatric hospital in Vietnam between 2013 and 2022.The primary outcome was in-hospital mortality in pediatric patients with DISH,which was defined as either aspartate aminotransferase>350 IU/L or alanine aminotransferase>400 IU/L.Prognostic models for estimating the risk of death among patients with DISH were developed using a predefined set of clinical covariables and hepatic biomarkers on PICU admission and during the first 72 hours of admission.Area under the curve,multivariable logistic regression,and multiple imputation using the chained equation for missing values were performed.Backward stepwise model selection based on the Akaike information criterion was employed.Bootstrapping,calibration slope,and Brier score were used to assess the final models.RESULTS A total of 459 children with DISH were included in the analysis.The median patient age was 7.7 years(interquartile range:4.3-10.1 years).The prevalence of dengue-associated PALF in children with DISH was 18.3%.Thirty-nine DISH patients developing PALF(8.5%)died.Hepatic biomarkers,including the international normalized ratio(INR)≥2.11 and total serum bilirubin(≥1.7 mg/dL),showed high predictive values for mortality(all P values<0.001).Multivariable models showed the significant clinical predictors of death from dengue-induced PALF in patients with DISH,including reduced level of consciousness(pain and unresponsive levels on the Alert,Verbal,Pain,Unresponsive scale),high vasoactive-inotropic score(>30),and elevated levels of blood lactate,INR,and serum bilirubin.The final prognostic model demonstrated high discrimination,Brier score,and an acceptable calibration slope.CONCLUSION The prevalence of PALF in children with DISH is 18.3%.We developed robust prognostic models to estimate the risk of death in hospitalized children with severe dengue-induced hepatitis.

Effects of intrapulmonary percussive ventilation on airway mucus clearance: A bench model

AIM To determine the ability of intrapulmonary percussive ventilation(IPV) to promote airway clearance in spontaneously breathing patients and those on mechanical ventilation.METHODS An artificial lung was used to simulate a spontaneously breathing patient(Group 1), and was then connected to a mechanical ventilator to simulate a patient on mechanical ventilation(Group 2). An 8.5 mm endotracheal tube(ETT) connected to the test lung, simulated the patient airway. Artificial mucus was instilled into the mid-portion of the ETT. A filter was attached at both ends of the ETT to collect the mucus displaced proximally(mouth-piece filter) and distally(lung filter). The IPV machine was attached to the proximal end of the ETT and was applied for 10-min each to Group 1 and 2. After each experiment, the weight of the various circuit components were determined and compared to their dry weights to calculate the weight of the displaced mucus.RESULTS In Group 1(spontaneously breathing model), 26.8% ± 3.1% of the simulated mucus was displaced proximally, compared to 0% in Group 2(the mechanically ventilated model) with a P-value of < 0.01. In fact, 17% ± 1.5% of the mucus in Group 2 remained in the mid-portion of the ETT where it was initially instilled and 80% ± 4.2% was displaced distally back towards the lung(P < 0.01). There was an overall statistically significant amount of mucusmovement proximally towards the mouth-piece in the spontaneously breathing(SB) patient. There was also an overall statistically significant amount of mucus movement distally back towards the lung in the mechanically ventilated(MV) model. In the mechanically ventilated model, no mucus was observed to move towards the proximal/mouth piece section of the ETT. CONCLUSION This bench model suggests that IPV is associated with displacement of mucus towards the proximal mouthpiece in the SB patient, and distally in the MV model.

Community-acquired pneumonia:The importance of the early detection of drug-resistant organisms

Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States.While community-acquired pneumonia(CAP)is generally considered an acute time-limited illness,it is associated with high long-term mortality,with nearly one-third of patients requiring hospitalization dying within one year.An increasing trend of detecting multidrug-resistant(MDR)organisms causing CAP has been observed,especially in the Western world.In this editorial,we discuss about a publication by Jatteppanavar et al which reported that a case of a MDR organism was the culprit in developing pneumonia,bacteremia,and infective endocarditis that led to the patient’s death.The early detection of these resistant organisms helps improve patient outcomes.Significant advances have been made in the biotechnological and research space,but preventive measures,diagnostic techniques,and treatment strategies need to be developed.

Community-acquired multidrug-resistant pneumonia,bacteraemia,and infective endocarditis:A case report

BACKGROUND The prevalence of multidrug-resistant(MDR)bacteria has increased globally,with extensive drug-resistant(XDR)bacteria posing a threat to patients.CASE SUMMARY This case report describes a young man admitted for suspected tropical fever infections who experienced rapid deterioration in health.Despite negative results for tropical fever infections,he had neutrophilic leucocytosis,acute kidney injury,and chest imaging findings suggestive of bilateral consolidations.On day two,he was diagnosed with infective endocarditis with possible rheumatic heart disease and MDR methicillin-resistant Staphylococcus aureus bacteraemia,and communityacquired pneumonia.Despite treatment with broad-spectrum antibiotics,he did not respond and succumbed to death on day five.CONCLUSION This case highlights that clinicians/public should be aware of MDR communityacquired pneumonia,bacteraemia,and endocarditis which ultimately culminate in high rates of morbidity and mortality.Early identification of pathogenic strain and prompt antibiotic treatment are a mainstay for the management and prevention of early fatalities.Simultaneously,route cause analysis of communityacquired MDR/XDR pathogens is a global need.

New avenues for reducing intensive care needs in patients with chronic spinal cord injury

Relatively soon after their accident, patients suffering a spinal cord injury(SCI) begin generally experiencing the development of significant, often life-threatening secondary complications. Many of which are associated with chronic physical inactivity-related immune function problems and increasing susceptibility to infection that repeatedly requires intensive care treatment. Therapies capable of repairing the spinal cord or restoring ambulation would normally prevent many of these problems but, as of now, there is no cure for SCI. Thus, management strategies and antibiotics remain the standard of care although antimicrobial resistance constitutes a significant challenge for patients with chronic SCI facing recurrent infections of the urinary tract and respiratory systems. Identifying alternative therapies capable of safe and potent actions upon these serious health concerns should therefore be considered a priority. This editorial presents some of the novel approaches currently in development for the prevention of specific infections after SCI. Among them, brain-permeable small molecule therapeutics acting centrally on spinal cord circuits that can augment respiratory capabilities or bladder functions. If eventually approved by regulatory authorities, some of these new avenues may potentially become clinically-relevant therapies capable of indirectly preventing the occurrence and/or severity of these lifethreatening complications in people with paraplegic or tetraplegic injuries.

Ayman Abd Al-maksoud Yousef, MD, Series Editor Prognostic categorization of intensive care septic patients

Sepsis is one of the leading worldwide causes of morbidity and mortality in critically-ill patients. Prediction of outcome in patients with sepsis requires repeated clinical interpretation of the patients' conditions, clinical assessment of tissue hypoxia and the use of severity scoring systems, because the prognostic categorization accuracy of severity scoring indices alone, is relatively poor. Generally, such categorization depends on the severity of the septic state, ranging from systemic inflammatory response to septic shock. Now, there is no gold standard for the clinical assessment of tissue hypoxia which can be achieved by both global and regional oxygen extractabilities, added to prognostic pro-inflammatory mediators. Because the technology used to identify the genetic make-up of the human being is rapidly advancing, the structure of 30 000 genes which make-up the human DNA bank is now known. This would allow easy prognostic categorization of critically-ill patients including those suffering from sepsis. The present review spots lights on the main severity scoring systems used for outcome prediction in septic patients. For morbidity prediction, it discusses the Multiple Organ Dysfunction score, the sequential organ failure assessment score, and the logistic organdysfunction score. For mortality/survival prediction, it discusses the Acute Physiology and Chronic Health Evaluation scores, the Therapeutic Intervention Scoring System, the Simplified acute physiology score and the Mortality Probability Models. An ideal severity scoring system for prognostic categorization of patients with systemic sepsis is far from being reached. Scoring systems should be used with repeated clinical interpretation of the patients' conditions, and the assessment of tissue hypoxia in order to attain satisfactory discriminative performance and calibration power.

Quality indicators in respiratory therapy

Quality indicators in healthcare refer to measurable and quantifiable parameters used to assess and monitor the performance,effectiveness,and safety of healthcare services.These indicators provide a systematic way to evaluate the quality of care offered,and thereby to identify areas for improvement and to ensure that patient care meets established standards and best practices.Respiratory therapists play a vital role in areas of clinical administration such as infection control practices and quality improvement initiatives.Quality indicators serve as essential metrics for respiratory therapy departments to assess and enhance the overall quality of care.By systematically tracking and analyzing indicators related to infection control,treatment effectiveness,and adherence to protocols,respiratory care practitioners can identify areas to improve and implement evidence-based changes.This article reviewed how to identify,implement,and monitor quality indicators specific to the respiratory therapy departments to set benchmarks and enhance patient outcomes.