Dataset Information

Vasopressin in hemorrhagic shock: a systematic review and meta-analysis of randomized animal trials.

ABSTRACT:

Objective

The latest European guidelines for the management of hemorrhagic shock suggest the use of vasopressors (norepinephrine) in order to restore an adequate mean arterial pressure when fluid resuscitation therapy fails to restore blood pressure. The administration of arginine vasopressin (AVP), or its analogue terlipressin, has been proposed as an alternative treatment in the early stages of hypovolemic shock.

Design

A meta-analysis of randomized controlled animal trials.

Participants

A total of 433 animals from 15 studies were included.

Interventions

The ability of AVP and terlipressin to reduce mortality when compared with fluid resuscitation therapy, other vasopressors (norepinephrine or epinephrine), or placebo was investigated.

Measurements and main results

Pooled estimates showed that AVP and terlipressin consistently and significantly improve survival in hemorrhagic shock (mortality: 26/174 (15%) in the AVP group versus 164/259 (63%) in the control arms; OR=0.09; 95% CI 0.05 to 0.15; P for effect<0.001; P for heterogeneity=0.30; I2=14%).

Conclusions

Results suggest that AVP and terlipressin improve survival in the early phases of animal models of hemorrhagic shock. Vasopressin seems to be more effective than all other treatments, including other vasopressor drugs. These results need to be confirmed by human clinical trials.

SUBMITTER: Cossu AP

PROVIDER: S-EPMC4165559 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Vasopressin in hemorrhagic shock: a systematic review and meta-analysis of randomized animal trials.

Cossu Andrea Pasquale AP Mura Paolo P De Giudici Lorenzo Matteo LM Puddu Daniela D Pasin Laura L Evangelista Maurizio M Xanthos Theodoros T Musu Mario M Finco Gabriele G

BioMed research international 20140901

<h4>Objective</h4>The latest European guidelines for the management of hemorrhagic shock suggest the use of vasopressors (norepinephrine) in order to restore an adequate mean arterial pressure when fluid resuscitation therapy fails to restore blood pressure. The administration of arginine vasopressin (AVP), or its analogue terlipressin, has been proposed as an alternative treatment in the early stages of hypovolemic shock.<h4>Design</h4>A meta-analysis of randomized controlled animal trials.<h4> ...[more]

PMID: 25254206

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Project description:IntroductionCatecholamines are the most used vasopressors in vasodilatory shock. However, the development of adrenergic hyposensitivity and the subsequent loss of catecholamine pressor activity necessitate the search for other options. Our aim was to evaluate the effects of vasopressin and its analog terlipressin compared with catecholamine infusion alone in vasodilatory shock.MethodsA systematic review and meta-analysis of publications between 1966 and 2011 was performed. The Medline and CENTRAL databases were searched for studies on vasopressin and terlipressin in critically ill patients. The meta-analysis was limited to randomized controlled trials evaluating the use of vasopressin and/or terlipressin compared with catecholamine in adult patients with vasodilatory shock. The assessed outcomes were: overall survival, changes in the hemodynamic and biochemical variables, a decrease of catecholamine requirements, and adverse events.ResultsNine trials covering 998 participants were included. A meta-analysis using a fixed-effect model showed a reduction in norepinephrine requirement among patients receiving terlipressin or vasopressin infusion compared with control (standardized mean difference, -1.58 (95% confidence interval, -1.73 to -1.44); P < 0.0001). Overall, vasopressin and terlipressin, as compared with norepinephrine, reduced mortality (relative risk (RR), 0.87 (0.77 to 0.99); P = 0.04). Vasopressin compared with norepinephrine decreased mortality in adult patients (RR, 0.87 (0.76 to 1.00); P = 0.05) and in patients with septic shock (42.5% vs. 49.2%, respectively; RR, 0.87 (0.75 to 1.00); P = 0.05; number needed to treat, 1 to 15). There was no difference in adverse events between the vasopressin and control groups (RR, 0.98 (0.65 to 1.47); P = 0.92).ConclusionsVasopressin use in vasodilatory shock is safe, associated with reduced mortality, and facilitates weaning of catecholamines. In patients with septic shock, use of vasopressin compared with norepinephrine may also decrease mortality.

Project description:BackgroundCurrent research suggests that administration of vasopressin to patients with uncontrolled hemorrhagic shock (UHS) can avoid the detrimental effects associated with aggressive fluid resuscitation. However, vasopressin has a short half-life of 10~35 minutes in in vivo use and precludes its use in the pre-hospital setting. To increase the half-life of vasopressin, we proposed to synthesize liposome-encapsulated vasopressin and test it in a rat model of UHS.MethodsThe film hydration method was used to prepare liposomal vasopressin consisting of: Dipalmitoylphosphatidylcholine, cholesterol, and dipalmitoyl phosphatidylethanolamine (20:20:1 mole ratio). 42 rats were subjected to UHS and randomly received 5 different treatments (vasopressin, liposomal vasopressin, lactate ringer (LR), liposome only and sham). Outcome of UHS were measured using 4 common prognostic tests: mean arterial pressure (MAP), serum lactate level, inflammatory profile and pulmonary edema.ResultsThe dynamic light scattering results confirmed that we had prepared a successful liposomal vasopressin complex. Comparing the serum vasopressin concentration of liposomal vasopressin and vasopressin treated animals by ELISA, we found that the concentration of vasopressin for the liposomal vasopressin treated group is higher at 60 minutes. However, there was no significant difference between the MAP profile of rats treated with vasopressin and liposomal vasopressin in UHS. We also observed that animals treated with liposomal vasopressin performed indifferently to vasopressin treated rats in serum lactate level, inflammatory profile and edema profile. For most of our assays, the liposome only control behaves similarly to LR resuscitation in UHS rats.ConclusionWe have synthesized a liposomal vasopressin complex that can prolong the serum concentration of vasopressin in a rat model of UHS. Although UHS rats treated with either liposomal vasopressin or vasopressin showed no statistical differences, it would be worthwhile to repeat the experiments with different liposomal compositions.

Project description:In 2012, the United States Food and Drug Administration (FDA) issued a warning regarding potential adverse effects of HMG-CoA reductase inhibitors (statins) on cognition, based on the Adverse Events Reporting System and a review of the medical literature. We aimed to synthesize randomized clinical trial (RCTs) evidence on the association between statin therapy and cognitive outcomes.We searched MEDLINE, EMBASE, and Cochrane CENTRAL through December 2012, and reviewed published systematic reviews of statin treatment. We sought RCTs that compared statin treatment versus placebo or standard care, and reported at least one cognitive outcome (frequency of adverse cognitive events or measurements using standard neuropsychological cognitive test scores). Studies reporting sufficient information to calculate effect sizes were included in meta-analyses. Standardized and unstandardized mean differences were calculated for continuous outcomes for global cognition and for pre-specified cognitive domains. The main outcome was change in cognition measured by neuropsychological tests; an outcome of secondary interest was the frequency of adverse cognitive events observed during follow-up.We identified 25 RCTs (all placebo-controlled) reporting cognitive outcomes in 46,836 subjects, of which 23 RCTs reported cognitive test results in 29,012 participants. Adverse cognitive outcomes attributable to statins were rarely reported in trials involving cognitively normal or impaired subjects. Furthermore, meta-analysis of cognitive test data (14 studies; 27,643 participants) failed to show significant adverse effects of statins on all tests of cognition in either cognitively normal subjects (standardized mean difference 0.01, 95% confidence interval, CI, -0.01 to 0.03, p?=?0.42) or Alzheimer's disease subjects (standardized mean difference -0.05, 95% CI -0.19 to 0.10, p?=?0.38).Statin therapy was not associated with cognitive impairment in RCTs. These results raise questions regarding the continued merit of the FDA warning about potential adverse effects of statins on cognition.

Project description:Background Thromboembolic and bleeding events after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are major public concerns leading to vaccine hesitancy. Due to low incidence, an individual randomized controlled trial (RCT) is underpowered to determine whether SARS-CoV-2 vaccines increase the risks of thromboembolism and hemorrhage. Methods We performed a literature search using PubMed, EMBASE, Cochrane, medRxiv databases, and reference lists of relevant articles to identify RCTs that reported thromboembolic, hemorrhagic events, and thromboembolism/hemorrhage-related death after SARS-CoV-2 vaccination. The primary aim of this systematic review and meta-analysis was to estimate the pooled thromboembolic risk related to SARS-CoV-2 vaccines compared to placebo. The secondary outcomes included estimating the risks of arterial thromboembolism (ATE), venous thromboembolisms (VTE), hemorrhage, thrombocytopenia, and thromboembolism/hemorrhage-related death. Results Eight RCTs of 4 vaccine platforms comprised of 195,196 participants were retrieved. SARS-CoV-2 vaccines were not associated with an increased risk of overall thromboembolism (risk ratio [RR], 1.14; 95% CI [confidence interval], 0.61–2.14; I2 = 35%), ATE (RR, 0.97; 95% CI, 0.46–2.06; I2 = 21%), VTE (RR, 1.47; 95% CI, 0.72–2.99; I2 = 0%), hemorrhage (RR, 0.97; 95% CI, 0.35–2.68; I2 = 0), and thromboembolism/hemorrhage-related death (RR, 0.53; 95% CI, 0.16–1.79; I2 = 0). Compared to the baseline estimated risk of these outcomes in participants administered placebos, the risk differences with vaccines were very small and not statistically significant. These findings were consistent in the subgroup analysis across 4 vaccine platforms. Conclusion Vaccines against SARS-CoV-2 are not associated with an increased risk of thromboembolism, hemorrhage, and thromboembolism/hemorrhage-related death. Supplementary Information The online version contains supplementary material available at 10.1186/s12959-021-00340-4.

Project description:IntroductionThe benefit of medications used in out-of-hospital, shock-refractory cardiac arrest remains controversial. This study aims to compare the treatment outcomes of medications for out-of-hospital, shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT).MethodsThe inclusion criteria were randomized controlled trials of participants older than eight years old who had atraumatic, out-of-hospital, shock-refractory VF/pVT in which at least one studied group received a medication. We conducted a database search on October 28, 2019, that included PubMed, Scopus, Web of Science, CINAHL Complete, and Cochrane CENTRAL. Citations of relevant meta-analyses were also searched. We performed frequentist network meta-analysis (NMA) to combine the comparisons. The outcomes were analyzed by using odds ratios (OR) and compared to placebo. The primary outcome was survival to hospital discharge. The secondary outcomes included the return of spontaneous circulation (ROSC), survival to hospital admission, and the neurological outcome at discharge. We ranked all outcomes using surface under the cumulative ranking score.ResultsWe included 18 studies with 6,582 participants. The NMA of 20 comparisons included 12 medications and placebo. Only norepinephrine showed a significant increase of ROSC (OR = 8.91, 95% confidence interval [CI], 1.88-42.29). Amiodarone significantly improved survival to hospital admission (OR = 1.53, 95% CI, 1.01-2.32). The ROSC and survival-to-hospital admission data were significantly heterogeneous with the I2 of 55.1% and 59.1%, respectively. This NMA satisfied the assumption of transitivity.ConclusionNo medication was associated with improved survival to hospital discharge from out-of-hospital, shock-refractory cardiac arrest. For the secondary outcomes, norepinephrine was associated with improved ROSC and amiodarone was associated with an increased likelihood of survival to hospital admission in the NMA.

Dataset Information

Vasopressin in hemorrhagic shock: a systematic review and meta-analysis of randomized animal trials.

Objective

Design

Participants

Interventions

Measurements and main results

Conclusions

Publications

Vasopressin in hemorrhagic shock: a systematic review and meta-analysis of randomized animal trials.

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