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Effects of Alprostadil Combined with Edaravone on Inflammation, Oxidative Stress and Pulmonary Function in Patients with Traumatic Hemorrhagic Shock
Luo, D., Pan, Q., Wang, L., Zhao, W., Bao, W.
Cellular and Molecular Biology (Noisy-Le-Grand, France). 2022;68(8):123-128
Abstract
The study aimed to explore the roles of alprostadil combined with edaravone in inflammation, oxidative stress and Pulmonary function in patients with traumatic hemorrhagic shock (HS). 80 patients with traumatic HS treated in Feicheng Hospital Affiliated to Shandong First Medical University and Tai'an City Central Hospital from January 2018 to January 2022 were enrolled and divided into observation group (n=40) and control group (n=40) according to the randomized control method. Patients in the control group were given alprostadil alone (5 g alprostadil + 10 mL normal saline) in addition to conventional treatment, while those in the observation group received edaravone (30 mg edaravone + 250 mL normal saline) on the basis of treatment in the control group. The patients in both groups were treated via intravenous infusion once a day for 5 days. 24 hours (h) after resuscitation, venous blood were collected to detect serum biochemical indicators such as blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Enzyme-linked immunosorbent assay (ELISA) was conducted to determine serum inflammatory factors. Lung lavage fluid was collected to examine pulmonaryfunction indicators such as myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9) activity and to observe the oxygenation index (OI). Blood pressure was measured at admission and 24 h after surgery. The observation group had significantly lowered serum BUN, AST and ALT (p<0.05), the content of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as well as oxidative stress indexes like superoxide dismutase (SOD) and malondialdehyde (MDA) (p<0.05) and pulmonary function indicators (p<0.05) but overtly increased content of SOD and OI. Furthermore, the blood pressure in the observation group dropped to 30 mmHg at admission and rose to the normal range. Alprostadil combined with edaravone effectively reduces inflammatory factors and improves oxidative stress and pulmonary function in patients with traumatic HS, whose efficacy is significantly better than that of alprostadil alone.
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Optimal timing of venous thromboembolic chemoprophylaxis initiation following blunt solid organ injury: meta-analysis and systematic review
Murphy, P. B., de Moya, M., Karam, B., Menard, L., Holder, E., Inaba, K., Schellenberg, M.
European Journal of Trauma and Emergency Surgery : Official Publication of the European Trauma Society. 2022;48(3):2039-2046
Abstract
PURPOSE The need to prevent venous thromboembolism (VTE) following blunt solid organ injury must be balanced against the concern for exacerbation of hemorrhage. The optimal timing for initiation of VTE chemoprophylaxis is not known. The objective was to determine the safety and efficacy of early (≤ 48 h) VTE chemoprophylaxis initiation following blunt solid organ injury. METHODS An electronic search was performed of medical libraries for English language studies on timing of VTE chemoprophylaxis initiation following blunt solid organ injury published from inception to April 2020. Included studies compared early (≤ 48 h) versus late (> 48 h) initiation of VTE chemoprophylaxis in adults with blunt splenic, liver, and/or kidney injury. Estimates were pooled using random-effects meta-analysis. Odds ratios were utilized to quantify differences in failure of nonoperative management, need for blood transfusion and rates of VTE. RESULTS The search identified 2,111 studies. Of these, ten studies comprising 14,675 patients were included. All studies were non-randomized and only one was prospective. The overall odds of failure of nonoperative management were no different between early and late groups, OR 1.09 (95%CI 0.92-1.29). Similarly, there was no difference in the need for blood transfusion either during overall hospital stay, OR 0.91 (95%CI 0.70-1.18), or post prophylaxis initiation, OR 1.23 (95%CI 0.55-2.73). There were significantly lower odds of VTE when patients received early VTE chemoprophylaxis, OR 0.51 (95%CI 0.33-0.81). CONCLUSIONS Patients undergoing nonoperative management for blunt solid organ injury can be safely and effectively prescribed early VTE chemoprophylaxis. This results in significantly lower VTE rates without demonstrable harm.
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Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial
Sims CA, Holena D, Kim P, Pascual J, Smith B, Martin N, Seamon M, Shiroff A, Raza S, Kaplan L, et al
JAMA surgery. 2019
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Abstract
Importance: Current therapies for traumatic blood loss focus on hemorrhage control and blood volume replacement. Severe hemorrhagic shock, however, is associated with a state of arginine vasopressin (AVP) deficiency, and supplementation of this hormone may decrease the need for blood products in resuscitation. Objective: To determine whether low-dose supplementation of AVP in patients with trauma (hereinafter referred to as trauma patients) and with hemorrhagic shock decreases their need for transfused blood products during resuscitation. Design, Setting, and Participants: This randomized, double-blind placebo-controlled clinical trial included adult trauma patients (aged 18-65 years) who received at least 6 U of any blood product within 12 hours of injury at a single urban level 1 trauma center from May 1, 2013, through May 31, 2017. Exclusion criteria consisted of prehospital cardiopulmonary resuscitation, emergency department thoracotomy, corticosteroid use, chronic renal insufficiency, coronary artery disease, traumatic brain injury requiring any neurosurgical intervention, pregnancy, prisoner status, or AVP administration before enrollment. Data were analyzed from May 1, 2013, through May 31, 2017, using intention to treat and per protocol. Interventions: After administration of an AVP bolus (4 U) or placebo, participants received AVP (≤0.04 U/min) or placebo for 48 hours to maintain a mean arterial blood pressure of at least 65 mm Hg. Main Outcomes: The primary outcome was total volume of blood product transfused. Secondary end points included total volume of crystalloid transfused, vasopressor requirements, secondary complications, and 30-day mortality. Results: One hundred patients underwent randomization (49 to the AVP group and 51 to the placebo group). Patients were primarily young (median age, 27 years [interquartile range {IQR}, 22-25 years]) and male (n = 93) with penetrating trauma (n = 79). Cohort characteristics before randomization were well balanced. At 48 hours, patients who received AVP required significantly less blood products (median, 1.4 [IQR, 0.5-2.6] vs 2.9 [IQR, 1.1-4.8] L; P = .01) but did not differ in requirements for crystalloids (median, 9.9 [IQR, 7.9-13.0] vs 11.0 [8.9-15.0] L; P = .22) or vasopressors (median, 400 [IQR, 0-5900] vs 1400 [IQR, 200-7600] equivalent units; P = .22). Although the groups had similar rates of mortality (6 of 49 [12%] vs 6 of 51 [12%]; P = .94) and total complications (24 of 44 [55%] vs 30 of 47 [64%]; P = .37), the AVP group had less deep venous thrombosis (5 of 44 [11%] vs 16 of 47 [34%]; P = .02). Conclusions and Relevance: Low-dose AVP during the resuscitation of trauma patients in hemorrhagic shock decreases blood product requirements. Additional research is necessary to determine whether including AVP improves morbidity or mortality. Trial Registration: ClinicalTrials.gov identifier: NCT01611935.
PICO Summary
Population
Adult trauma patients who received at least 6 U of any blood product within 12 hours of injury at a single urban level 1 trauma center (n=100).
Intervention
Arginine vasopressin (AVP) bolus (4 U)) for 48 hours to maintain a mean arterial blood pressure of at least 65 mm Hg. (n=49).
Comparison
Placebo (n=51).
Outcome
At 48 hours, patients who received AVP required significantly less blood products but did not differ in requirements for crystalloids or vasopressors. Although the groups had similar rates of mortality (12% vs 12%) and total complications (55%vs 64%), the AVP group had less deep venous thrombosis (11%vs 34%).
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Randomized trial to assess safety and clinical efficacy of intensive blood pressure reduction in acute spontaneous intracerebral haemorrhage
Gupta S, Abbot A K, Srinath R, Tewari A K, Gupta A, Gorthi S P, Narayanan C S, Totlani S I, Sirohi Y S, Anadure R
Medical Journal, Armed Forces India. 2018;74((2)):120-125.
Abstract
Background: Haematoma expansion due to raised blood pressure in spontaneous intracerebral haemorrhage may determine outcome. The aim of this study was to determine safety and efficacy of lowering blood pressure in acute spontaneous intracerebral haemorrhage. Methods: This open label, multicentric trial randomized patients ≥18 years with spontaneous intracerebral haemorrhage with no secondary cause within 72 h of onset to tight BP control arm where treatment was initiated if mean arterial pressure (MAP) was ≥115 mm of Hg and conventional BP control arm where treatment was initiated if MAP was ≥130 mm of Hg. The MAP was maintained in the respective arm for another 72 h after which both arms had MAP below 115 mm of Hg. Primary outcome was modified Rankin Scale at 90 days. Results: 118 patients, 59 in each arm were included. Follow up was available for all. Baseline characteristics were similar. At 90 days there was no significant difference between median mRS between the two arms. Odds Ratio for "poor outcome" (mRS 3-6) in the tight control arm (safety of the intervention) against "good outcome" (mRS 0-2) was not significant (OR 0.70 [95% CI 0.34-1.47] p = 0.35). Efficacy of the intervention in the form of Odds Ratio for "good outcome" in the tight control arm was not significant (OR 1.43 [95% CI 0.68-2.99], p = 0.35). Conclusion: In patients with spontaneous intracerebral haemorrhage who present within 72 h of the onset of symptoms, MAP can be safely lowered if it crosses 115 mm of Hg but it does not improve clinical outcome.
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WITHDRAWN: Haemostatic drugs for traumatic brain injury
Perel P, Roberts I, Shakur H, Thinkhamrop B, Phuenpathom N, Yutthakasemsunt S
Cochrane Database of Systematic Reviews. 2010;((1):):CD007877.
Abstract
BACKGROUND Traumatic brain injury (TBI) is a leading cause of death and disability. Intracranial bleeding is a common complication of TBI, and intracranial bleeding can develop or worsen after hospital admission. Haemostatic drugs may reduce the occurrence or size of intracranial bleeds and consequently lower the morbidity and mortality associated with TBI. OBJECTIVES To assess the effects of haemostatic drugs on mortality, disability and thrombotic complications in patients with traumatic brain injury. SEARCH STRATEGY We searched the electronic databases: Cochrane Injuries Group Specialised Register (3 February 2009), CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (1950 to Week 3 2009), PubMed (searched 3 February 2009 (last 180 days)), EMBASE (1980 to Week 4 2009), CINAHL (1982 to January 2009), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2009). SELECTION CRITERIA We included published and unpublished randomised controlled trials comparing haemostatic drugs (antifibrinolytics: aprotinin, tranexamic acid (TXA), aminocaproic acid or recombined activated factor VIIa (rFVIIa)) with placebo, no treatment, or other treatment in patients with acute traumatic brain injury. DATA COLLECTION AND ANALYSIS Two review authors independently examined all electronic records, and extracted the data. We judged that there was clinical heterogeneity between trials so we did not attempt to pool the results of the included trials. The results are reported separately. MAIN RESULTS We included two trials. One was a post-hoc analysis of 30 TBI patients from a randomised controlled trial of rFVIIa in blunt trauma patients. The risk ratio for mortality at 30 days was 0.64 (95% CI 0.25 to 1.63) for rFVIIa compared to placebo. This result should be considered with caution as the subgroup analysis was not pre-specified for the trial. The other trial evaluated the effect of rFVIIa in 97 TBI patients with evidence of intracerebral bleeding in a computed tomography (CT) scan. The corresponding risk ratio for mortality at the last follow up was 1.08 (95% CI 0.44 to 2.68). The quality of the reporting of both trials was poor so it was difficult to assess the risk of bias. AUTHORS' CONCLUSIONS There is no reliable evidence from randomised controlled trials to support the effectiveness of haemostatic drugs in reducing mortality or disability in patients with TBI. New randomised controlled trials assessing the effects of haemostatic drugs in TBI patients should be conducted. These trials should be large enough to detect clinically plausible treatment effects.