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Acta Neuropsychiatrica Jan 2020Gene-environment (GxE) interactions may comprise an important part of the aetiology of depression, and childhood maltreatment (CM), a significant stressor, has...
OBJECTIVE
Gene-environment (GxE) interactions may comprise an important part of the aetiology of depression, and childhood maltreatment (CM), a significant stressor, has consistently been linked to depression. Hence, in this systematic review, we aimed to investigate the interaction between hypothalamus-pituitary-adrenal axis (HPA-axis) genes and CM in depression.
METHODS
We conducted a literature search using the Pubmed, Embase, and PsychINFO databases in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies investigating GxE interactions between HPA-axis genes [Angiotensin Converting Enzyme (ACE), Arginine Vasopressin (AVP), Corticotrophin Releasing Hormone (CRH), Corticotrophin Releasing Hormone Receptor 1 (CRHR1), Corticotrophin Releasing Hormone Receptor 2 (CRHR2), FK506 binding protein (FKBP5), Nuclear Receptor subfamily 3 group C member 1 (NR3C1), Nuclear Receptor subfamily 3 group C member 2 (NR3C2)] and CM in depression.
RESULTS
The literature search identified 159 potentially relevant studies. Following screening, 138 of these were excluded. Thus, 21 studies, investigating a total of 51 single nucleotide polymorphisms, were included in the final study. The most prevalent genes in the current study were CRHR1 and FKBP5. Significant GxE interactions were reported in seven of eight studies for CRHR1:rs110402 and CM, and in five of eight studies for FKBP5:rs1360780 and CM. In summary, our results suggest possible GxE interactions between CRHR1, FKBP5, NR3C1, and NR3C2 and CM, respectively. For the remaining genes, no relevant literature emerged.
CONCLUSIONS
We find that genetic variation in four HPA-axis genes may influence the effects of CM in depression.
PubMed: 31902387
DOI: 10.1017/neu.2020.1 -
Frontiers in Psychiatry 2019Autism spectrum disorder (ASD) is found in virtually all population groups regardless of ethnic or socioeconomic backgrounds. Among others, dominant symptoms of autism...
Systematic Review of Literature on Single-Nucleotide Polymorphisms Within the Oxytocin and Vasopressin Receptor Genes in the Development of Social Cognition Dysfunctions in Individuals Suffering From Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is found in virtually all population groups regardless of ethnic or socioeconomic backgrounds. Among others, dominant symptoms of autism persistent throughout its course of development include, inter alia, qualitative disorders of social communication and social interactions. Numerous studies have been performed on animal models as well as groups of healthy individuals to assess the potential role of oxytocinergic and vasopresynergic systems in normal social functioning. These studies have also discussed their potential participation in the development of social cognition dysfunctions in the course of ASD. This literature review aimed to identify studies examining single-nucleotide polymorphisms of the oxytocin (OXT) and arginine vasopressin (AVP) receptor genes and their differential effects on social cognitive dysfunction in the development of ASD. A systematic review of literature published within the last 10 years and accessible in PubMed, Google Scholar, Cochrane Library, and APA PsycNET databases was conducted by each author separately. Inclusion criteria required that articles should 1) be published between January 2008 and August 2018; 2) be published in English or Polish; 3) be located in periodical publications; 4) focus on the role of polymorphisms within oxytocin and vasopressin receptor genes in autistic population; 5) provide a clear presentation of the applied methodology; and 6) apply proper methodology. From the 491 studies qualified to the initial abstract analysis, 15 met the six inclusion criteria and were included in the full-text review. The analysis of available literature seems to indicate that there is an association between social cognition dysfunctions in the course of autism and selected alleles of polymorphisms within the OXT receptor AVP 1A receptor genes. However, previous studies neither specify the nature of this association in an unequivocal way nor select genotypes that are the basis for this association.
PubMed: 31214061
DOI: 10.3389/fpsyt.2019.00380 -
Acta Neuropsychiatrica Aug 2019Depression is a disorder caused by genetics and environmental factors. The aim of this study was to perform a review investigating the interaction between genetic...
OBJECTIVE
Depression is a disorder caused by genetics and environmental factors. The aim of this study was to perform a review investigating the interaction between genetic variations located in genes involved in hypothalamus-pituitary-adrenal axis (HPA-axis) and stressful life events (SLEs) in depression.
METHODS
In this systematic review, we selected articles investigating the interaction between genes involved in the HPA-axis, such as Arginine Vasopressin (AVP), Angiotensin Converting Enzyme (ACE), Corticotrophin Releasing Hormone (CRH), Corticotrophin Releasing Hormone Receptor 1 (CRHR1), Corticotrophin Releasing Hormone Receptor 2 (CRHR2), FK506 binding protein (FKBP5), Nuclear Receptor subfamily 3 group C member 1 (NR3C1), Nuclear Receptor subfamily 3 group C member 2 (NR3C2), and SLE. The literature search was conducted using the Pubmed, Embase, and PsychINFO databases in adherence with the PRISMA guidelines.
RESULTS
The search yielded 48 potentially relevant studies, of which 40 were excluded following screening. Eight studies were included in the final review. A total of 97 single nucleotide polymorphisms (SNPs) were examined in the eight included studies. The most prevalent gene was FKBP5, and the best studied polymorphism was FKBP5:rs1360780. Two of the five studies reported significant gene-environment (G × E) interactions between rs1360780 and SLE. Overall, four studies reported significant G × E interactions between FKBP5, CRH, or CRHR1 and SLE, respectively. No significant G × E interactions were found for the remaining genes.
CONCLUSIONS
Our results suggest that genetic variation in three genes in the HPA-axis possibly moderate the effects of SLEs in depression.
Topics: Depressive Disorder; Gene-Environment Interaction; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Polymorphism, Single Nucleotide; Stress, Psychological; Tacrolimus Binding Proteins
PubMed: 31106715
DOI: 10.1017/neu.2019.16 -
Critical Care (London, England) Mar 2019The aim of this study was to evaluate the effects and safety of vasopressin receptor agonists in patients with septic shock. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to evaluate the effects and safety of vasopressin receptor agonists in patients with septic shock.
METHODS
PubMed, EMBASE, and Cochrane library were searched for randomized controlled trials evaluating the effects of vasopressin receptor agonists in septic shock patients. Two reviewers performed literature selection, data extraction, and quality evaluation independently. The primary outcome was mortality. And secondary outcomes included intensive care unit (ICU) length of stay, duration of mechanical ventilation, and incidence of adverse events. In addition, a trial sequential analysis (TSA) was performed.
RESULTS
Twenty studies were eligible for meta-analysis. The results showed vasopressin receptor agonists use was associated with reduced mortality (relative risk (RR) 0.92; 95% confidence interval (CI) 0.84 to 0.99; I = 0%). Nevertheless, they had no significant effects on ICU length of stay (mean deviation (MD) - 0.08, 95% CI, - 0.68 to 0.52, I = 0%) and duration of mechanical ventilation (MD - 0.58, 95% CI - 1.47 to 0.31, I = 57%). Additionally, there was no significant difference in total adverse events between two groups (RR 1.28, 95% CI 0.87 to 1.90, I = 57%), but vasopressin receptor agonists administration could significantly increase the risk of digital ischemia (RR 4.85, 95% CI 2.81 to 8.39, I = 26%). Finally, there was no statistical difference of cardiovascular events (RR 0.91, 95% CI 0.53 to 1.57, I = 1%), arrhythmia (0.77, 95% CI 0.48 to 1.23, I = 23%), mesenteric ischemia (0.83, 95% CI 0.44 to 1.55, I = 0%), diarrhea (2.47, 95% CI 0.77 to 7.96, I = 49%), cerebrovascular events (1.36, 95% CI 0.18 to 10.54, I = 0%), and hyponatremia (1.47, 95% CI 0.84 to 2.55, I = 0%) between two groups. Egger's test showed there was no significant publication bias among studies (P = 0.36).
CONCLUSIONS
The use of vasopressin might result in reduced mortality in patients with septic shock. An increased risk of digital ischemia must be taken into account.
Topics: Hospital Mortality; Humans; Length of Stay; Patient Safety; Receptors, Vasopressin; Shock, Septic; Vasopressins
PubMed: 30871607
DOI: 10.1186/s13054-019-2362-4 -
Journal of Cardiac Surgery Jan 2019Arginine vasopressin (AVP) is a naturally occurring peptide with diverse effects mediated through selective V1 and V2 receptors. About 10% of patients undergoing...
BACKGROUND
Arginine vasopressin (AVP) is a naturally occurring peptide with diverse effects mediated through selective V1 and V2 receptors. About 10% of patients undergoing cardiopulmonary bypass develop postoperative vasodilatory shock requiring high-dose catecholamines. We sought to examine the role of AVP therapy in cardiac surgery.
METHODS
A search of Medline was conducted through September 2018 using key words and medical subject headings (MeSH) relating to AVP, copeptin, and cardiac surgery. A systematic review was performed on articles as they pertained to AVP for use as a vasopressor after cardiovascular surgery complicated by vasodilatory shock.
RESULTS
A relative or absolute deficiency of Arginine vasopressin is associated with vasodilatory shock after cardiopulmonary bypass. Physiologic replacement with exogenous Arginine vasopressin results in significant increases in systemic vascular resistance and mean arterial pressure with decreased requirements of catecholamines. At doses of <0.1 U/min Arginine vasopressin is safe with very few adverse effects.
CONCLUSION
Post-cardiopulmonary bypass vasodilatory shock is largely due to a relative deficiency of Arginine vasopressin. Exogenous administration of low-dose Arginine vasopressin alone or in combination with traditional catecholamines is a safe and effective way to manage this type of vasodilatory shock.
Topics: Cardiac Surgical Procedures; Humans; Shock, Surgical; Vasoconstrictor Agents; Vasodilation; Vasopressins
PubMed: 30597665
DOI: 10.1111/jocs.13968 -
Neuroscience and Biobehavioral Reviews Jan 2019Around 50% of depressed patients do not respond to antidepressants. Evidence from familial studies suggests a genetic component to this. This study investigated whether...
OBJECTIVE
Around 50% of depressed patients do not respond to antidepressants. Evidence from familial studies suggests a genetic component to this. This study investigated whether patients with polymorphisms in genes related to the hypothalamic-pituitary-adrenal (HPA) axis were less likely to respond to antidepressants.
METHOD
EMBASE, MEDLINE, PsycINFO, and the Cochrane Library were searched. Inclusionary criteria were: 1) patients with depression, 2) study of HPA axis-related candidate genes, 3) at least four weeks of antidepressants, and 4) assessment of depressive symptoms dividing patients into non-responders and responders.
RESULTS
Nineteen studies were identified. Non-responders and responders did not differ in single nucleotide polymorphisms (SNPs) in genes encoding arginine vasopressin. Findings were equivocal regarding genes encoding the FK506 binding protein 5 and glucocorticoid and mineralocorticoid receptors. Specific SNPs and haplotypes within genes related to corticotropin-releasing hormone (CRHBP, CRHR1) and melanocortins (POMC) predicted non-responder status.
CONCLUSIONS
Replication studies and additional investigations exploring gene x environment and drug x environment interactions are necessary before pharmacological treatments may be adjusted based on a patient's genetic profile.
Topics: Antidepressive Agents; Depression; Depressive Disorder; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Polymorphism, Genetic
PubMed: 30465786
DOI: 10.1016/j.neubiorev.2018.11.009 -
The Cochrane Database of Systematic... Sep 2018People with thrombocytopenia often require a surgical procedure. A low platelet count is a relative contraindication to surgery due to the risk of bleeding. Platelet... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with thrombocytopenia often require a surgical procedure. A low platelet count is a relative contraindication to surgery due to the risk of bleeding. Platelet transfusions are used in clinical practice to prevent and treat bleeding in people with thrombocytopenia. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to surgery. Alternatives to platelet transfusion are also used prior surgery.
OBJECTIVES
To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count.
SEARCH METHODS
We searched the following major data bases: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), PubMed (e-publications only), Ovid MEDLINE, Ovid Embase, the Transfusion Evidence Library and ongoing trial databases to 11 December 2017.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs), as well as non-RCTs and controlled before-and-after studies (CBAs), that met Cochrane EPOC (Effective Practice and Organisation of Care) criteria, that involved the transfusion of platelets prior to surgery (any dose, at any time, single or multiple) in people with low platelet counts. We excluded studies on people with a low platelet count who were actively bleeding.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane for data collection. We were only able to combine data for two outcomes and we presented the rest of the findings in a narrative form.
MAIN RESULTS
We identified five RCTs, all conducted in adults; there were no eligible non-randomised studies. Three completed trials enrolled 180 adults and two ongoing trials aim to include 627 participants. The completed trials were conducted between 2005 and 2009. The two ongoing trials are scheduled to complete recruitment by October 2019. One trial compared prophylactic platelet transfusions to no transfusion in people with thrombocytopenia in an intensive care unit (ICU). Two small trials, 108 participants, compared prophylactic platelet transfusions to other alternative treatments in people with liver disease. One trial compared desmopressin to fresh frozen plasma or one unit of platelet transfusion or both prior to surgery. The second trial compared platelet transfusion prior to surgery with two types of thrombopoietin mimetics: romiplostim and eltrombopag. None of the included trials were free from methodological bias. No included trials compared different platelet count thresholds for administering a prophylactic platelet transfusion prior to surgery. None of the included trials reported on all the review outcomes and the overall quality per reported outcome was very low.None of the three completed trials reported: all-cause mortality at 90 days post surgery; mortality secondary to bleeding, thromboembolism or infection; number of red cell or platelet transfusions per participant; length of hospital stay; or quality of life.None of the trials included children or people who needed major surgery or emergency surgical procedures.Platelet transfusion versus no platelet transfusion (1 trial, 72 participants)We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on all-cause mortality within 30 days (1 trial, 72 participants; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.41 to 1.45; very-low quality evidence). We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on the risk of major (1 trial, 64 participants; RR 1.60, 95% CI 0.29 to 8.92; very low-quality evidence), or minor bleeding (1 trial, 64 participants; RR 1.29, 95% CI 0.90 to 1.85; very-low quality evidence). No serious adverse events occurred in either study arm (1 trial, 72 participants, very low-quality evidence).Platelet transfusion versus alternative to platelet transfusion (2 trials, 108 participants)We were very uncertain whether giving a platelet transfusion prior to surgery compared to an alternative has any effect on the risk of major (2 trials, 108 participants; no events; very low-quality evidence), or minor bleeding (desmopressin: 1 trial, 36 participants; RR 0.89, 95% CI 0.06 to 13.23; very-low quality evidence: thrombopoietin mimetics: 1 trial, 65 participants; no events; very-low quality evidence). We were very uncertain whether there was a difference in transfusion-related adverse effects between the platelet transfused group and the alternative treatment group (desmopressin: 1 trial, 36 participants; RR 2.70, 95% CI 0.12 to 62.17; very-low quality evidence).
AUTHORS' CONCLUSIONS
Findings of this review were based on three small trials involving minor surgery in adults with thrombocytopenia. We found insufficient evidence to recommend the administration of preprocedure prophylactic platelet transfusions in this situation with a lack of evidence that transfusion resulted in a reduction in postoperative bleeding or all-cause mortality. The small number of trials meeting the inclusion criteria and the limitation in reported outcomes across the trials precluded meta-analysis for most outcomes. Further adequately powered trials, in people of all ages, of prophylactic platelet transfusions compared with no transfusion, other alternative treatments, and considering different platelet thresholds prior to planned and emergency surgical procedures are required. Future trials should include major surgery and report on bleeding, adverse effects, mortality (as a long-term outcome) after surgery, duration of hospital stay and quality of life measures.
Topics: Adult; Benzoates; Deamino Arginine Vasopressin; Hemostatics; Humans; Hydrazines; Plasma; Platelet Transfusion; Postoperative Care; Postoperative Hemorrhage; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin
PubMed: 30221749
DOI: 10.1002/14651858.CD012779.pub2 -
Physiology & Behavior Nov 2018The risk of developing stress related disorders such as depression is two times higher in women than in men, and social stress is considered the principal etiology for...
The risk of developing stress related disorders such as depression is two times higher in women than in men, and social stress is considered the principal etiology for this disorder. Social defeat animal model is the most common procedure to induce social stress in male rodents, but the stressful stimulus and the stress response can be different for each sex. In this regard, social defeat stress model does not fit the social nature of females, and according to the emerging evidence, the social instability stress (SIS) model could be a suitable procedure to investigate this stress related disorder in females. This study aims to systematically review the effects of SIS on physiological and behavioral parameters involved in the pathophysiology of depression, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method on PubMed, Medline and Web of Science. Seventeen studies met the inclusion criteria. The reported physiological measures comprised the hypothalamic-pituitary-adrenal axis activity, neurotrophic factors, immune and monoaminergic systems, vasopressin and oxytocin receptors, sex hormone levels and estrus cycle, while main behavioral measures involved sucrose preference test, forced swimming test, elevated plus maze, open field test and social interaction. This systematic review revealed a wide variability on the social instability regimen and on the measured variables. However, all studies agree that SIS model can elicit behavioral and physiological alteration involved in stress related disorders, with HPA axis hyperactivity, increased anxiety-like behavior and disrupted reward system being the most repeated outcomes. A unified SIS application criterion is required in order to obtain consistent data and elucidate the underlying mechanisms of anxiety and depression in females.
Topics: Animals; Disease Models, Animal; Female; Mental Disorders; Rodentia; Social Behavior; Stress, Psychological
PubMed: 30196085
DOI: 10.1016/j.physbeh.2018.09.001 -
The Cochrane Database of Systematic... Jun 2018Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain.
OBJECTIVES
This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 1 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also screened the reference lists of potentially relevant studies, contacted authors, and screened the websites of regulatory agencies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of any intervention with placebo, no treatment, standard care, or any other intervention in patients with chronic non-hypovolaemic hypotonic hyponatraemia. We also included subgroups with hyponatraemia from studies with broader inclusion criteria (e.g. people with chronic heart failure or people with cirrhosis with or without hyponatraemia), provided we could obtain outcomes for participants with hyponatraemia from the report or the study authors.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. We expressed treatment effects as mean difference (MD) for continuous outcomes (health-related quality of life, length of hospital stay, change from baseline in serum sodium concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes (death, response and rapid increase in serum sodium concentration, hypernatraemia, polyuria, hypotension, acute kidney injury, liver function abnormalities) together with 95% confidence intervals (CI).
MAIN RESULTS
We identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189 participants) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11, 95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision; and on health-related quality of life because results are at serious risk of performance, selective reporting and attrition bias, and suffer from indirectness related to the validity of the Short Form Health Survey (SF-12) in the setting of hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low certainty evidence due to risk of performance bias and imprecision) (3 studies, 610 participants: MD -1.63 days, 95% CI -2.96 to -0.30), and may make little or no difference to cognitive function (low certainty evidence due to indirectness and imprecision). Vasopressin receptor antagonists probably increase the intermediate outcome of serum sodium concentration (21 studies, 2641 participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (moderate certainty evidence due to risk of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18). But they probably also increase the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (moderate certainty evidence due to indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and commonly cause side-effects such as thirst (13 studies, 1666 participants: OR 2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69, 95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity remains uncertain due to large imprecision. Effects were generally consistent across the different agents, suggesting class effect.Data for other interventions such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids, demeclocycline, lithium and phenytoin were largely absent.
AUTHORS' CONCLUSIONS
In people with chronic hyponatraemia, vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3% increased risk of it being rapid. To date there is very low certainty evidence for patient-important outcomes; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm; there does not appear to be an important effect on cognitive function, but hospital stay may be slightly shorter, although available data are limited. Treatment decisions must weigh the value of an increase in serum sodium concentration against its short-term risks and unknown effects on patient-important outcomes. Evidence for other treatments is largely absent.Further studies assessing standard treatments such as fluid restriction or urea against placebo and one-another would inform practice and are warranted. Given the limited available evidence for patient-important outcomes, any study should include these outcomes in a standardised manner.
Topics: Antidiuretic Hormone Receptor Antagonists; Chronic Disease; Humans; Hyponatremia; Length of Stay; Quality of Life; Randomized Controlled Trials as Topic; Sodium
PubMed: 29953167
DOI: 10.1002/14651858.CD010965.pub2 -
JAMA May 2018Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock-a condition due to excessive vasodilation, most frequently from severe... (Comparative Study)
Comparative Study Meta-Analysis Review
Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-analysis.
IMPORTANCE
Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock-a condition due to excessive vasodilation, most frequently from severe infection. Blood pressure support with a noncatecholamine vasopressor may reduce stimulation of adrenergic receptors and decrease myocardial oxygen demand. Atrial fibrillation is common with catecholamines and is associated with adverse events, including mortality and increased length of stay (LOS).
OBJECTIVES
To determine whether treatment with vasopressin + catecholamine vasopressors compared with catecholamine vasopressors alone was associated with reductions in the risk of adverse events.
DATA SOURCES
MEDLINE, EMBASE, and CENTRAL were searched from inception to February 2018. Experts were asked and meta-registries searched to identify ongoing trials.
STUDY SELECTION
Pairs of reviewers identified randomized clinical trials comparing vasopressin in combination with catecholamine vasopressors to catecholamines alone for patients with distributive shock.
DATA EXTRACTION AND SYNTHESIS
Two reviewers abstracted data independently. A random-effects model was used to combine data.
MAIN OUTCOMES AND MEASURES
The primary outcome was atrial fibrillation. Other outcomes included mortality, requirement for renal replacement therapy (RRT), myocardial injury, ventricular arrhythmia, stroke, and LOS in the intensive care unit and hospital. Measures of association are reported as risk ratios (RRs) for clinical outcomes and mean differences for LOS.
RESULTS
Twenty-three randomized clinical trials were identified (3088 patients; mean age, 61.1 years [14.2]; women, 45.3%). High-quality evidence supported a lower risk of atrial fibrillation associated with vasopressin treatment (RR, 0.77 [95% CI, 0.67 to 0.88]; risk difference [RD], -0.06 [95% CI, -0.13 to 0.01]). For mortality, the overall RR estimate was 0.89 (95% CI, 0.82 to 0.97; RD, -0.04 [95% CI, -0.07 to 0.00]); however, when limited to trials at low risk of bias, the RR estimate was 0.96 (95% CI, 0.84 to 1.11). The overall RR estimate for RRT was 0.74 (95% CI, 0.51 to 1.08; RD, -0.07 [95% CI, -0.12 to -0.01]). However, in an analysis limited to trials at low risk of bias, RR was 0.70 (95% CI, 0.53 to 0.92, P for interaction = .77). There were no significant differences in the pooled risks for other outcomes.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the addition of vasopressin to catecholamine vasopressors compared with catecholamines alone was associated with a lower risk of atrial fibrillation. Findings for secondary outcomes varied.
Topics: Atrial Fibrillation; Catecholamines; Drug Therapy, Combination; Female; Humans; Length of Stay; Male; Publication Bias; Shock; Vasoconstrictor Agents; Vasopressins
PubMed: 29801010
DOI: 10.1001/jama.2018.4528