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Chest Nov 2023This review discusses the rationale for vasopressin use, summarizes the results of clinical trials evaluating vasopressin, and focuses on the timing of vasopressin... (Review)
Review
TOPIC IMPORTANCE
This review discusses the rationale for vasopressin use, summarizes the results of clinical trials evaluating vasopressin, and focuses on the timing of vasopressin initiation to provide clinicians guidance for optimal adjunctive vasopressin initiation in patients with septic shock.
REVIEW FINDINGS
Patients with septic shock require vasoactive agents to restore adequate tissue perfusion. After norepinephrine, vasopressin is the suggested second-line adjunctive agent in patients with persistent inadequate mean arterial pressure. Vasopressin use in practice is heterogeneous likely because of inconsistent clinical trial findings, the lack of specific recommendations for when it should be used, and the high drug acquisition cost. Despite these limitations, vasopressin has demonstrated price inelastic demand, and its use in the United States has continued to increase. However, questions remain regarding optimal vasopressin use in patients with septic shock, particularly regarding patient selection and the timing of vasopressin initiation.
SUMMARY
Experimental studies evaluating the initiation timing of vasopressin in patients with septic shock are limited, and recent observational studies have revealed an association between vasopressin initiation at lower norepinephrine-equivalent doses or lower lactate concentrations and lower mortality.
Topics: Humans; United States; Vasoconstrictor Agents; Shock, Septic; Vasopressins; Norepinephrine; Arterial Pressure
PubMed: 37479058
DOI: 10.1016/j.chest.2023.07.009 -
Nature Medicine Nov 2018Sepsis is the third leading cause of death worldwide and the main cause of mortality in hospitals, but the best treatment strategy remains uncertain. In particular,...
Sepsis is the third leading cause of death worldwide and the main cause of mortality in hospitals, but the best treatment strategy remains uncertain. In particular, evidence suggests that current practices in the administration of intravenous fluids and vasopressors are suboptimal and likely induce harm in a proportion of patients. To tackle this sequential decision-making problem, we developed a reinforcement learning agent, the Artificial Intelligence (AI) Clinician, which extracted implicit knowledge from an amount of patient data that exceeds by many-fold the life-time experience of human clinicians and learned optimal treatment by analyzing a myriad of (mostly suboptimal) treatment decisions. We demonstrate that the value of the AI Clinician's selected treatment is on average reliably higher than human clinicians. In a large validation cohort independent of the training data, mortality was lowest in patients for whom clinicians' actual doses matched the AI decisions. Our model provides individualized and clinically interpretable treatment decisions for sepsis that could improve patient outcomes.
Topics: Administration, Intravenous; Artificial Intelligence; Clinical Decision-Making; Cohort Studies; Critical Care; Female; Humans; Learning; Male; Sepsis; Software; Vasoconstrictor Agents
PubMed: 30349085
DOI: 10.1038/s41591-018-0213-5 -
Clinical Journal of the American... Nov 2022AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal...
AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C-associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.
Topics: Humans; Hepatorenal Syndrome; Antiviral Agents; Biomarkers; Hepatitis C, Chronic; Acute Kidney Injury; Liver Cirrhosis; Vasoconstrictor Agents; Nephritis, Interstitial
PubMed: 35902128
DOI: 10.2215/CJN.03040322 -
Intensive Care Medicine Oct 2020ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine,... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial.
PURPOSE
ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement.
METHODS
In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates.
RESULTS
Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02).
CONCLUSION
Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.
Topics: Adult; Australia; Humans; Hypotension; Intensive Care Units; Midodrine; Vasoconstrictor Agents
PubMed: 32885276
DOI: 10.1007/s00134-020-06216-x -
Critical Care (London, England) Jan 2023Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line... (Review)
Review
Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line vasopressor and vasopressin as the second-line vasopressor. In clinical practice, due to drug availability, local practice variations, special settings, and ongoing research, several alternative vasoconstrictors and adjuncts are used in the absence of precise equivalent doses. Norepinephrine equivalence (NEE) is frequently used in clinical trials to overcome this heterogeneity and describe vasopressor support in a standardized manner. NEE quantifies the total amount of vasopressors, considering the potency of each such agent, which typically includes catecholamines, derivatives, and vasopressin. Intensive care studies use NEE as an eligibility criterion and also an outcome measure. On the other hand, NEE has several pitfalls which clinicians should know, important the lack of conversion of novel vasopressors such as angiotensin II and also adjuncts such as methylene blue, including a lack of high-quality data to support the equation and validate its predictive performance in all types of critical care practice. This review describes the history of NEE and suggests an updated formula incorporating novel vasopressors and adjuncts.
Topics: Humans; Norepinephrine; Shock, Septic; Shock; Vasoconstrictor Agents; Vasopressins; Critical Care
PubMed: 36670410
DOI: 10.1186/s13054-023-04322-y -
Archives of Disease in Childhood. Fetal... Jul 2021In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary... (Review)
Review
In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary shunts (patent ductus arteriosus and patent foramen value) allow for right-to-left shunting and hypoxaemia. Systemic hypotension can occur in newborns with PPHN due to variety of reasons, such as enhanced peripheral vasodilation, impaired left ventricular function and decreased preload. Systemic hypotension can lead to end organ injury from poor perfusion and hypoxaemia in the newborn with PPHN. Thus, it must be managed swiftly. However, not all newborns with PPHN and systemic hypotension can be managed the same way. Individualised approach based on physiology and echocardiographic findings are necessary to improve perfusion to essential organs. Here we present a review of the physiology and mechanisms of systemic hypotension in PPHN, which can then guide treatment.
Topics: Blood Pressure Monitors; Extracorporeal Membrane Oxygenation; Fluid Therapy; Hemodynamics; Humans; Hypotension; Infant, Newborn; Persistent Fetal Circulation Syndrome; Practice Guidelines as Topic; Vasoconstrictor Agents
PubMed: 33478959
DOI: 10.1136/archdischild-2020-319705 -
The Journal of Evidence-based Dental... Jun 2021Coronary disease and Hypertension are highly prevalent health problems worldwide, with the latter being one of the most common diseases in patients visiting dental... (Review)
Review
BACKGROUND
Coronary disease and Hypertension are highly prevalent health problems worldwide, with the latter being one of the most common diseases in patients visiting dental clinics. Local anesthetics (LAs) with vasoconstrictor agents (VC) are known to be commonly used in dental practice. For the above-mentioned reasons, dentists should know how to adapt and treat patients with these hazardous conditions.
OBJECTIVE
The aim of this study was to find out if the use of local anesthetics (LAs) in combination with vasoconstrictor (VC) agents in dental treatment presents a risk in patient with a known history of Hypertension and/or Coronary disease.
MATERIALS AND METHODS
This systematic review was conducted in accordance with The PRISMA guidelines and registered on the PROSPERO database (CRD42020187369). The search strategy was based on Mesh terms, Boolean operator AND, and the PICO model. It was designed to identify all the randomized clinical trials (RCTs) published in the last 30 years, which assessed whether the use of LA with VC agents in dental treatment produces a significant increase/decrease in hemodynamics in patients with known history of Hypertension and/or Coronary disease. The Cochrane Collaboration's tool was used to assess risk of bias of the included RCTs.
RESULTS
An initial electronic search resulted in 87 papers; however only 9 RCTs met the inclusion criteria. There was a total of 482 subjects (N = 482), of which 412 had a known history of Hypertension or Coronary disease.
CONCLUSIONS
According to the literature reviewed, the use of 1 to 2 cartridges of local anesthetics with 1:80,000, 1:100,000 or 1:200,000 epinephrine in patients with controlled Hypertension and/ or Coronary disease is safe. Randomized clinical trials are essential in determining the safety or risks associated with the use of LAs with VC agents in patients with poorly controlled Hypertension and Coronary disease.
Topics: Anesthetics, Local; Coronary Artery Disease; Dental Care; Humans; Hypertension; Vasoconstrictor Agents
PubMed: 34391560
DOI: 10.1016/j.jebdp.2021.101569 -
American Journal of Respiratory and... Aug 2022Cardiovascular instability/collapse is a common peri-intubation event in patients who are critically ill. To identify potentially modifiable variables associated with... (Observational Study)
Observational Study
Cardiovascular instability/collapse is a common peri-intubation event in patients who are critically ill. To identify potentially modifiable variables associated with peri-intubation cardiovascular instability/collapse (i.e., systolic arterial pressure <65 mm Hg [once] or <90 mm Hg for >30 minutes; new/increased vasopressor requirement; fluid bolus >15 ml/kg, or cardiac arrest). INTUBE (International Observational Study to Understand the Impact and Best Practices of Airway Management In Critically Ill Patients) was a multicenter prospective cohort study of patients who were critically ill and undergoing tracheal intubation in a convenience sample of 197 sites from 29 countries across five continents from October 1, 2018, to July 31, 2019. A total of 2,760 patients were included in this analysis. Peri-intubation cardiovascular instability/collapse occurred in 1,199 out of 2,760 patients (43.4%). Variables associated with this event were older age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02-1.03), higher heart rate (OR, 1.008; 95% CI, 1.004-1.012), lower systolic blood pressure (OR, 0.98; 95% CI, 0.98-0.99), lower oxygen saturation as measured by pulse oximetry/Fi before induction (OR, 0.998; 95% CI, 0.997-0.999), and the use of propofol as an induction agent (OR, 1.28; 95% CI, 1.05-1.57). Patients with peri-intubation cardiovascular instability/collapse were at a higher risk of ICU mortality with an adjusted OR of 2.47 (95% CI, 1.72-3.55), < 0.001. The inverse probability of treatment weighting method identified the use of propofol as the only factor independently associated with cardiovascular instability/collapse (OR, 1.23; 95% CI, 1.02-1.49). When administered before induction, vasopressors (OR, 1.33; 95% CI, 0.84-2.11) or fluid boluses (OR, 1.17; 95% CI, 0.96-1.44) did not reduce the incidence of cardiovascular instability/collapse. Peri-intubation cardiovascular instability/collapse was associated with an increased risk of both ICU and 28-day mortality. The use of propofol for induction was identified as a modifiable intervention significantly associated with cardiovascular instability/collapse.Clinical trial registered with clinicaltrials.gov (NCT03616054).
Topics: Critical Illness; Humans; Intubation, Intratracheal; Propofol; Prospective Studies; Shock; Vasoconstrictor Agents
PubMed: 35536310
DOI: 10.1164/rccm.202111-2575OC -
Surgical Infections 2018Sepsis accounts for 10% of intensive care unit admissions and significant healthcare costs. Although the mortality rate from sepsis has been decreasing with better... (Review)
Review
BACKGROUND
Sepsis accounts for 10% of intensive care unit admissions and significant healthcare costs. Although the mortality rate from sepsis has been decreasing with better critical care, early identification of septic patients, and prompt interventions, the mortality rate remains 20%-30%.
METHOD
Review of the English-language literature.
RESULTS
Norepinephrine is the first-line vasopressor in shock and is associated with a lower mortality rate as well as fewer adverse effects. Dopamine has similar actions but is associated with significantly more tachydysrhythmias and should be reserved for patients with bradycardia. Epinephrine and vasopressin are appropriate second-line vasopressors and may enable use of lower doses of norepinephrine while improving hemodynamics. Inotropes may be added in patients with cardiac dysfunction.
CONCLUSION
Appropriate treatment of sepsis includes prompt identification, early antimicrobial drug therapy, appropriate fluid resuscitation, and initiation of vasopressors in the presence of continued septic shock. Further research needs to be done to better understand the ideal timing of the addition of a second agent and the optimal combinations of vasopressors for individual patients.
Topics: Dopamine; Epinephrine; Humans; Norepinephrine; Sepsis; Shock; Vasoconstrictor Agents
PubMed: 29336676
DOI: 10.1089/sur.2017.255 -
Anesthesia and Analgesia Oct 2022Cardiac surgery-associated acute kidney injury (CS-AKI) is common and is associated with increased risk for postoperative morbidity and mortality. Our recent survey of... (Meta-Analysis)
Meta-Analysis Review
Cardiac surgery-associated acute kidney injury (CS-AKI) is common and is associated with increased risk for postoperative morbidity and mortality. Our recent survey of the Society of Cardiovascular Anesthesiologists (SCA) membership showed 6 potentially renoprotective strategies for which clinicians would most value an evidence-based review (ie, intraoperative target blood pressure, choice of specific vasopressor agent, erythrocyte transfusion threshold, use of alpha-2 agonists, goal-directed oxygen delivery on cardiopulmonary bypass [CPB], and the "Kidney Disease Improving Global Outcomes [KDIGO] bundle of care"). Thus, the SCA's Continuing Practice Improvement Acute Kidney Injury Working Group aimed to provide a practice update for each of these strategies in cardiac surgical patients based on the evidence from randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane library databases were comprehensively searched for eligible studies from inception through February 2021, with search results updated in August 2021. A total of 15 RCTs investigating the effects of the above-mentioned strategies on CS-AKI were included for meta-analysis. For each strategy, the level of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Across the 6 potentially renoprotective strategies evaluated, current evidence for their use was rated as "moderate," "low," or "very low." Based on eligible RCTs, our analysis suggested using goal-directed oxygen delivery on CPB and the "KDIGO bundle of care" in high-risk patients to prevent CS-AKI (moderate level of GRADE evidence). Our results suggested considering the use of vasopressin in vasoplegic shock patients to reduce CS-AKI (low level of GRADE evidence). The decision to use a restrictive versus liberal strategy for perioperative red cell transfusion should not be based on concerns for renal protection (a moderate level of GRADE evidence). In addition, targeting a higher mean arterial pressure during CPB, perioperative use of dopamine, and use of dexmedetomidine did not reduce CS-AKI (a low or very low level of GRADE evidence). This review will help clinicians provide evidence-based care, targeting improved renal outcomes in adult patients undergoing cardiac surgery.
Topics: Acute Kidney Injury; Adult; Anesthesiologists; Cardiac Surgical Procedures; Dexmedetomidine; Dopamine; Humans; Oxygen; Vasoconstrictor Agents
PubMed: 35544772
DOI: 10.1213/ANE.0000000000006068