Intravenous(IV)vasopressors are essential in the management of hypotension and shock.Initiation of oral vasoactive agents to facilitate weaning of IV vasopressors to liberate patients from the intensive care unit is c...Intravenous(IV)vasopressors are essential in the management of hypotension and shock.Initiation of oral vasoactive agents to facilitate weaning of IV vasopressors to liberate patients from the intensive care unit is common despite conflicting evidence regarding the benefits of this practice.While midodrine appears to be the most frequently studied oral vasoactive agent for this purpose,its adverse effect profile may preclude its use in certain populations.In addition,some patients may require persistent use of IV vasopressors for hypotension refractory to midodrine.The use of additional and alternative oral vasoactive agents bearing different mechanisms of action is emerging.This article provides a comprehensive review of the pharmacology,clinical uses,dosing strategies,and safety considerations of oral vasoactive agents and their application in the inten-sive care setting.展开更多
BACKGROUND Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit(ICU),with prolonged use increasing risk of withdrawal symptoms...BACKGROUND Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit(ICU),with prolonged use increasing risk of withdrawal symptoms upon sudden discontinuation.As clonidine is an enterally available alpha-2A adrenergic agonist,it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal syndromes.The appropriate dosing and conversion strategies for using enteral clonidine in this context are not known.The objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal symptoms.AIM To systematically review the practice,dosing schema,and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill adults.METHODS This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults(≥18 years).Randomized controlled trials,prospective cohorts,and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were included.The primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine withdrawal.Other secondary outcomes included prevalence of adverse events associated with enteral clonidine use,re-initiation of dexmedetomidine,duration of mechanical ventilation,and ICU length of stay.RESULTS A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 patients.All three studies were observational,two being prospective and one retrospective.In all included studies,the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the physician.Weaning time ranged from 13 to 167 h on average.Enteral clonidine was started in the prospective studies in a similar protocolized method,with 0.3 mg every 6 h.After starting clonidine,patients remained on dexmedetomidine for a median of 1-28 h.Following the termination of dexmedetomidine,two trials tapered enteral clonidine by increasing the interval every 24 h from 6 h to 8h,12h,and 24 h,followed by clonidine discontinuation.For indicators of enteral clonidine withdrawal,the previously tolerable dosage was reinstated for several days before resuming the taper on the same protocol.The adverse events associated with enteral clonidine use were higher than patients on dexmedetomidine taper alone with increased agitation.The re-initiation of dexmedetomidine was not documented in any study.Only 17(37%)patients were mechanically ventilated with median duration of 3.5 d for 13 patients in one of the 2 studies.ICU lengths of stay were similar.CONCLUSION Enteral clonidine is a strategy to wean critically ill patients from dexmedetomidine.There is an association of increased withdrawal symptoms and agitation with the use of a clonidine taper.展开更多
The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century.Recently,a paradigm shift is observed as volatile anesthetics extend...The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century.Recently,a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres,finding diverse applications in intensive care settings.In the dynamic landscape of intensive care,volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements,managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus,conditions of high sedative requirements including burns,high opioid or alcohol use and neurological conditions such as status epilepticus.Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry,providing intensivists with multiple options to tailor therapy.Furthermore,their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy,mitigating risks associated with conventional sedation modalities.Despite the amounting enthusiasm for the use of these therapies,barriers to widespread utilization include expanding equipment availability,staff familiarity and training of safe use.This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology,administration considerations in intensive care settings,complication considerations,and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.展开更多
Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite...Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite early antimicrobial therapy and lung protective mechanical ventilation. Both clinical entities are characterized by acute pulmonary inflammation in response to direct or indirect lung injury. Adjunct anti-inflammatory treatment with corticosteroids is increasingly used, although the evidence for benefit is limited. The treatment decisions are based on radiographic, clinical and physiological variables without regards to inflammatory state. Current evidence suggests a role of biomarkers for the assessment of severity, and distinguishing sub-phenotypes (hyperinflammatory versus hypo-inflammatory) with important prognostic and therapeutic implications. Although many inflammatory biomarkers have been studied the most common and of interest are C-reactive protein, procalcitonin, and pro-inflammatory cytokines including interleukin 6. While extensively studied as prognostic tools (prognostic enrichment), limited data are available for the role of biomarkers in determining appropriate initiation, timing and dosing of adjunct anti-inflammatory treatment (predictive enrichment)展开更多
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 ...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.展开更多
The number of patients receiving hematopoietic stem cell transplantation(HSCT) is rapidly rising worldwide. Despite substantial improvements in peri-transplant care, pulmonary complications resulting in respiratory fa...The number of patients receiving hematopoietic stem cell transplantation(HSCT) is rapidly rising worldwide. Despite substantial improvements in peri-transplant care, pulmonary complications resulting in respiratory failure remain a major contributor to morbidity and mortality in the post-transplant period, and represent a major barrier to the overall success of HSCT. Infectious complications include pneumonia due to bacteria, viruses, and fungi, and most commonly occur during neutropenia in the early post-transplant period. Non-infectious complications include idiopathic pneumonia syndrome, periengraftment respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary veno-occlusive disease, delayed pulmonary toxicity syndrome, cryptogenic organizing pneumonia, bronchiolitis obliterans syndrome, and post-transplant lymphoproliferative disorder. These complications have distinct clinical features and risk factors, occur at differing times following transplant, and contribute to morbidity and mortality.展开更多
Methicillin-resistant Staphylococcus aureus(MRSA)has remained a major threat to healthcare;in both hospital and community settings over the past five decades.With the current use of antibiotics for a variety of infect...Methicillin-resistant Staphylococcus aureus(MRSA)has remained a major threat to healthcare;in both hospital and community settings over the past five decades.With the current use of antibiotics for a variety of infections,including MRSA,emerging resistance is a major concern.Currently available treatments have restrictions limiting their use.These issues include,but are not limited to,side effects,cross-resistance,lack of understanding of pharmacokinetics and clinical pharmacodynamics,gradual increment in minimal inhibitory concentration over the period(MIC creep)and ineffectiveness in dealing with bacterial biofilms.Despite availability of various therapeutic options for MRSA,the clinical cure rates remain low with high morbidity and mortality.Given these challenges with existing treatments,there is a need for development of novel agents for MRSA.Along with prompt infection control strategies and strict implementation of antibiotic stewardship,cautious use of newer anti-MRSA agents will be of utmost importance.This article reviews the treatments and limitations of MRSA management and highlights the future path.展开更多
BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is oftenresistant to conventional therapies for shock. Norepinephrine and epinephrine arestandards of care for vasoplegic shock, but vaso...BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is oftenresistant to conventional therapies for shock. Norepinephrine and epinephrine arestandards of care for vasoplegic shock, but vasopressin has increasingly been usedas a primary pressor in vasoplegic shock because of its unique pharmacology andlack of inotropic activity. It remains unclear whether vasopressin has distinctbenefits over standard of care for patients with vasoplegic shock.AIMTo summarize the available literature evaluating vasopressin vs non-vasopressinalternatives on the clinical and patient-centered outcomes of vasoplegic shock inadult intensive care unit (ICU) patients.METHODSThis was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegicshock after cardiac surgery. Randomized controlled trials, prospective cohorts,and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine,methylene blue, hydroxocobalamin, or other pressors were included. The primaryoutcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke,ICU length of stay, duration of vasopressor therapy, incidence of acute kidneyinjury stage II-III, and mechanical ventilation for greater than 48 h.RESULTSA total of 1161 studies were screened for inclusion with 3 meeting inclusioncriteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality,stroke, ventricular arrhythmias, and duration of mechanical ventilation weresimilar between groups. Conflicting results were observed for acute kidney injurystage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of staywith higher certainty of evidence in favor of vasopressin serving a protective rolefor these outcomes.CONCLUSIONVasopressin was not found to be superior to alternative pressor therapy for any ofthe included outcomes. Results are limited by mixed methodologies, small overallsample size, and heterogenous populations.展开更多
文摘Intravenous(IV)vasopressors are essential in the management of hypotension and shock.Initiation of oral vasoactive agents to facilitate weaning of IV vasopressors to liberate patients from the intensive care unit is common despite conflicting evidence regarding the benefits of this practice.While midodrine appears to be the most frequently studied oral vasoactive agent for this purpose,its adverse effect profile may preclude its use in certain populations.In addition,some patients may require persistent use of IV vasopressors for hypotension refractory to midodrine.The use of additional and alternative oral vasoactive agents bearing different mechanisms of action is emerging.This article provides a comprehensive review of the pharmacology,clinical uses,dosing strategies,and safety considerations of oral vasoactive agents and their application in the inten-sive care setting.
文摘BACKGROUND Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit(ICU),with prolonged use increasing risk of withdrawal symptoms upon sudden discontinuation.As clonidine is an enterally available alpha-2A adrenergic agonist,it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal syndromes.The appropriate dosing and conversion strategies for using enteral clonidine in this context are not known.The objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal symptoms.AIM To systematically review the practice,dosing schema,and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill adults.METHODS This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults(≥18 years).Randomized controlled trials,prospective cohorts,and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were included.The primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine withdrawal.Other secondary outcomes included prevalence of adverse events associated with enteral clonidine use,re-initiation of dexmedetomidine,duration of mechanical ventilation,and ICU length of stay.RESULTS A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 patients.All three studies were observational,two being prospective and one retrospective.In all included studies,the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the physician.Weaning time ranged from 13 to 167 h on average.Enteral clonidine was started in the prospective studies in a similar protocolized method,with 0.3 mg every 6 h.After starting clonidine,patients remained on dexmedetomidine for a median of 1-28 h.Following the termination of dexmedetomidine,two trials tapered enteral clonidine by increasing the interval every 24 h from 6 h to 8h,12h,and 24 h,followed by clonidine discontinuation.For indicators of enteral clonidine withdrawal,the previously tolerable dosage was reinstated for several days before resuming the taper on the same protocol.The adverse events associated with enteral clonidine use were higher than patients on dexmedetomidine taper alone with increased agitation.The re-initiation of dexmedetomidine was not documented in any study.Only 17(37%)patients were mechanically ventilated with median duration of 3.5 d for 13 patients in one of the 2 studies.ICU lengths of stay were similar.CONCLUSION Enteral clonidine is a strategy to wean critically ill patients from dexmedetomidine.There is an association of increased withdrawal symptoms and agitation with the use of a clonidine taper.
文摘The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century.Recently,a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres,finding diverse applications in intensive care settings.In the dynamic landscape of intensive care,volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements,managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus,conditions of high sedative requirements including burns,high opioid or alcohol use and neurological conditions such as status epilepticus.Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry,providing intensivists with multiple options to tailor therapy.Furthermore,their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy,mitigating risks associated with conventional sedation modalities.Despite the amounting enthusiasm for the use of these therapies,barriers to widespread utilization include expanding equipment availability,staff familiarity and training of safe use.This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology,administration considerations in intensive care settings,complication considerations,and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.
文摘Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite early antimicrobial therapy and lung protective mechanical ventilation. Both clinical entities are characterized by acute pulmonary inflammation in response to direct or indirect lung injury. Adjunct anti-inflammatory treatment with corticosteroids is increasingly used, although the evidence for benefit is limited. The treatment decisions are based on radiographic, clinical and physiological variables without regards to inflammatory state. Current evidence suggests a role of biomarkers for the assessment of severity, and distinguishing sub-phenotypes (hyperinflammatory versus hypo-inflammatory) with important prognostic and therapeutic implications. Although many inflammatory biomarkers have been studied the most common and of interest are C-reactive protein, procalcitonin, and pro-inflammatory cytokines including interleukin 6. While extensively studied as prognostic tools (prognostic enrichment), limited data are available for the role of biomarkers in determining appropriate initiation, timing and dosing of adjunct anti-inflammatory treatment (predictive enrichment)
文摘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.
文摘The number of patients receiving hematopoietic stem cell transplantation(HSCT) is rapidly rising worldwide. Despite substantial improvements in peri-transplant care, pulmonary complications resulting in respiratory failure remain a major contributor to morbidity and mortality in the post-transplant period, and represent a major barrier to the overall success of HSCT. Infectious complications include pneumonia due to bacteria, viruses, and fungi, and most commonly occur during neutropenia in the early post-transplant period. Non-infectious complications include idiopathic pneumonia syndrome, periengraftment respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary veno-occlusive disease, delayed pulmonary toxicity syndrome, cryptogenic organizing pneumonia, bronchiolitis obliterans syndrome, and post-transplant lymphoproliferative disorder. These complications have distinct clinical features and risk factors, occur at differing times following transplant, and contribute to morbidity and mortality.
文摘Methicillin-resistant Staphylococcus aureus(MRSA)has remained a major threat to healthcare;in both hospital and community settings over the past five decades.With the current use of antibiotics for a variety of infections,including MRSA,emerging resistance is a major concern.Currently available treatments have restrictions limiting their use.These issues include,but are not limited to,side effects,cross-resistance,lack of understanding of pharmacokinetics and clinical pharmacodynamics,gradual increment in minimal inhibitory concentration over the period(MIC creep)and ineffectiveness in dealing with bacterial biofilms.Despite availability of various therapeutic options for MRSA,the clinical cure rates remain low with high morbidity and mortality.Given these challenges with existing treatments,there is a need for development of novel agents for MRSA.Along with prompt infection control strategies and strict implementation of antibiotic stewardship,cautious use of newer anti-MRSA agents will be of utmost importance.This article reviews the treatments and limitations of MRSA management and highlights the future path.
文摘BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is oftenresistant to conventional therapies for shock. Norepinephrine and epinephrine arestandards of care for vasoplegic shock, but vasopressin has increasingly been usedas a primary pressor in vasoplegic shock because of its unique pharmacology andlack of inotropic activity. It remains unclear whether vasopressin has distinctbenefits over standard of care for patients with vasoplegic shock.AIMTo summarize the available literature evaluating vasopressin vs non-vasopressinalternatives on the clinical and patient-centered outcomes of vasoplegic shock inadult intensive care unit (ICU) patients.METHODSThis was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegicshock after cardiac surgery. Randomized controlled trials, prospective cohorts,and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine,methylene blue, hydroxocobalamin, or other pressors were included. The primaryoutcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke,ICU length of stay, duration of vasopressor therapy, incidence of acute kidneyinjury stage II-III, and mechanical ventilation for greater than 48 h.RESULTSA total of 1161 studies were screened for inclusion with 3 meeting inclusioncriteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality,stroke, ventricular arrhythmias, and duration of mechanical ventilation weresimilar between groups. Conflicting results were observed for acute kidney injurystage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of staywith higher certainty of evidence in favor of vasopressin serving a protective rolefor these outcomes.CONCLUSIONVasopressin was not found to be superior to alternative pressor therapy for any ofthe included outcomes. Results are limited by mixed methodologies, small overallsample size, and heterogenous populations.