Efficacy of Acyclovir to Suppress Herpes Simplex Virus Oropharyngeal Reactivation in Patients Who Are Mechanically Ventilated: An Ancillary Study of the Preemptive Treatment for Herpesviridae (PTH) Trial.
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SUBMITTER: Luyt CE
PROVIDER: S-EPMC8689380 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Importance:The role of herpes simplex virus (HSV) reactivation on morbidity and mortality in patients in the intensive care unit requiring mechanical ventilation remains unknown. Objective:To determine whether preemptive treatment with intravenous acyclovir reduces the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation. Design, Setting, and Participants:A double-blind, placebo-controlled randomized clinical trial was conducted in 16 intensive care units in France. Participants included 239 adults (age, >18 years) who received mechanical ventilation for at least 96 hours and continued to receive mechanical ventilation for 48 hours or more, with HSV oropharyngeal reactivation. Patients were enrolled between February 2, 2014, and February 22, 2018. Interventions:Participants were randomized to receive intravenous acyclovir, 5 mg/kg, 3 times daily for 14 days or a matching placebo. Main Outcomes and Measures:The primary end point was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included mortality at 60 days. Main analyses were conducted on an intention-to-treat basis. Results:Of 239 patients enrolled and randomized, 1 patient withdrew consent, leaving 238 patients, with 119 patients in both the acyclovir and placebo (control) groups (median [IQR] age, 61 [50-70] years; 76 [32%] women) available for primary outcome measurement. On day 60, the median (IQR) numbers of ventilator-free days were 35 (0-53) for acyclovir recipients and 36 (0-50]) for controls (P?=?.17 for between-group comparison). Among secondary outcomes, 26 patients (22%) and 39 patients (33%) had died at day 60 (risk difference, 0.11, 95% CI, -0.004 to 0.22, P?=?.06). The adverse event frequency was similar for both groups (28% in the acyclovir group and 23% in the placebo group, P?=?.40), particularly acute renal failure post randomization affecting 3 acyclovir recipients (3%) and 2 controls (2%). Four patients (3%) in the acyclovir group vs none in the placebo group stopped the study drug for treatment-related adverse events. Conclusions and Relevance:In patients receiving mechanical ventilation for 96 hours or more with HSV reactivation in the throat, use of acyclovir, 5 mg/kg, 3 times daily for 14 days, did not increase the number of ventilator-free days at day 60, compared with placebo. These findings do not appear to support routine preemptive use of acyclovir in this setting. Trial Registration:ClinicalTrials.gov identifier: NCT02152358.
| S-EPMC6990840 | biostudies-literature
Project description:BackgroundThe effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation.MethodsThis double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults???18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for???48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n?=?39) or a matching placebo (n?=?37).ResultsThe primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N?=?39) compared with control patients (N?=?37) was 1.14 (95% CI from 0.63 to 2.06; P?=?0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0-51] and 0 [0-43] days, respectively (P?=?0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P?=?.845). Creatinine levels and blood cells counts did not differ significantly between the two groups.ConclusionsIn patients mechanically ventilated for???96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.
| S-EPMC7876264 | biostudies-literature
Project description:IntroductionStudies indicate that mechanically ventilated patients develop significant diaphragm muscle weakness, but the etiology of weakness and its clinical impact remain incompletely understood. We assessed diaphragm strength in mechanically ventilated medical ICU patients, correlated the development of diaphragm weakness with multiple clinical parameters, and examined the relationship between the level of diaphragm weakness and patient outcomes.MethodsTransdiaphragmatic twitch pressure (PdiTw) in response to bilateral magnetic stimulation of the phrenic nerves was measured. Diaphragm weakness was correlated with the presence of infection, blood urea nitrogen, albumin, and glucose levels. The relationship of diaphragm strength to patient outcomes, including mortality and the duration of mechanical ventilation for successfully weaned patients, was also assessed.ResultsWe found that infection is a major risk factor for diaphragm weakness in mechanically ventilated medical ICU patients. Outcomes for patients with severe diaphragm weakness (PdiTw<10 cmH2O) were poor, with a markedly increased mortality (49%) compared to patients with PdiTw?10 cmH2O (7% mortality, P=0.022). In addition, survivors with PdiTw<10 cmH2O required a significantly longer duration of mechanical ventilation (12.3±1.7 days) than those with PdiTw?10 cmH2O (5.5±2.0 days, P=0.016).ConclusionsInfection is a major cause of severe diaphragm weakness in mechanically ventilated patients. Moreover, diaphragm weakness is an important determinant of poor outcomes in this patient population.
| S-EPMC3840677 | biostudies-literature
Project description:PurposeDiaphragm weakness induced by mechanical ventilation may contribute to difficult weaning from the ventilator. For optimal force generation the muscle proteins myosin and titin are indispensable. The present study investigated if myosin and titin loss or dysfunction are involved in mechanical ventilation-induced diaphragm weakness.MethodsMale Wistar rats were either assigned to a control group (n = 10) or submitted to 18 h of mechanical ventilation (MV, n = 10). At the end of the experiment, diaphragm and soleus muscle were excised for functional and biochemical analysis.ResultsMaximal specific active force generation of muscle fibers isolated from the diaphragm of MV rats was lower than controls (128 ± 9 vs. 165 ± 13 mN/mm(2), p = 0.02) and was accompanied by a proportional reduction of myosin heavy chain concentration in these fibers. Passive force generation upon stretch was significantly reduced in diaphragm fibers from MV rats by ca. 35%. Yet, titin content was not significantly different between control and MV diaphragm. In vitro pre-incubation with phosphatase-1 decreased passive force generation upon stretch in diaphragm fibers from control, but not from MV rats. Mechanical ventilation did not affect active or passive force generation in the soleus muscle.ConclusionsMechanical ventilation leads to impaired diaphragm fiber active force-generating capacity and passive force generation upon stretch. Loss of myosin contributes to reduced active force generation, whereas reduced passive force generation is likely to result from a decreased phosphorylation status of titin. These impairments were not discernable in the soleus muscle of 18 h mechanically ventilated rats.
| S-EPMC3308006 | biostudies-literature
Project description:BackgroundTracheostomy is used for patients who require prolonged mechanical ventilation. Extensive research has described the provision and optimal timing of tracheostomy, but very little describes tracheostomy utilization in low- and middle-income countries, particularly in sub-Saharan Africa.MethodsThis prospective cohort study describes patients admitted to the intensive care unit (ICU) of a tertiary hospital in Malawi who received tracheostomy versus those who did not, with a primary outcome of hospital mortality. We performed subgroup analysis of patients with severe head injuries.ResultsThe analysis included 451 patients admitted to the study ICU between September 2016 and July 2018. Overall hospital mortality was 40% for patients who received tracheostomy and 63% for patients who did not. Logistic regression modeling revealed an odds ratio (OR) of 0.34 (95% CI 0.18-0.64) for hospital mortality among patients who received tracheostomy versus those who did not (p < 0.001). Standardized mortality ratio weighting revealed an odds ratio of 0.81 (95% CI 0.65-0.99, p < 0.001) for hospital death among patients who received tracheostomy versus those who did not. In the subgroup excluding severe head injury, both ICU (50%) and hospital mortality (75%) were higher overall, but hospital mortality was not more common for patients with tracheostomy versus without (OR 1.28, 95% CI 0.94-1.74, p = 0.104).ConclusionsTracheostomy is not associated with hospital mortality in a Malawi ICU cohort, but these results are affected by the presence of head injury. Research may focus on home tracheostomy care given the lack of hospital discharge options for patients in austere settings.
| S-EPMC8171994 | biostudies-literature
Project description:Assessing and managing pain and agitation in critically ill children can be challenging. Multiple factors contribute to the challenges of management, including prior medication exposure, surgical and procedural interventions, pharmacokinetics, and age-related pharmacodynamics making the population heterogeneous. Therefore, individualizing treatment approaches embedded with frequent assessments is likely to improve the management of pain and agitation in critically ill children. Novel approaches to manage pain and agitation continue to evolve and will require ongoing evaluation prior to widespread adoption.
| S-EPMC6513151 | biostudies-literature
Project description:ObjectivesThe determinants of decisions to limit life support (withholding or withdrawal) in ventilated stroke patients have been evaluated mainly for patients with intracranial hemorrhages. We aimed to evaluate the frequency of life support limitations in ventilated ischemic and hemorrhagic stroke patients compared with a nonbrain-injured population and to determine factors associated with such decisions.DesignMulticenter prospective French observational study.SettingFourteen ICUs of the French OutcomeRea network.PatientsFrom 2005 to 2016, we included stroke patients and nonbrain-injured patients requiring invasive ventilation within 24 hours of ICU admission.InterventionNone.Measurements and main resultsWe identified 373 stroke patients (ischemic, n = 167 [45%]; hemorrhagic, n = 206 [55%]) and 5,683 nonbrain-injured patients. Decisions to limit life support were taken in 41% of ischemic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.59 [95% CI, 2.78-4.65]) and in 33% of hemorrhagic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.9 [95% CI, 2.97-5.11]). Time from ICU admission to the first limitation was longer in ischemic than in hemorrhagic stroke (5 [3-9] vs 2 d [1-6] d; p < 0.01). Limitation of life support preceded ICU death in 70% of ischemic strokes and 45% of hemorrhagic strokes (p < 0.01). Life support limitations in ischemic stroke were increased by a vertebrobasilar location (vs anterior circulation, subdistribution hazard ratio, 1.61 [95% CI, 1.01-2.59]) and a prestroke modified Rankin score greater than 2 (2.38 [1.27-4.55]). In hemorrhagic stroke, an age greater than 70 years (2.29 [1.43-3.69]) and a Glasgow Coma Scale score less than 8 (2.15 [1.08-4.3]) were associated with an increased risk of limitation, whereas a higher nonneurologic admission Sequential Organ Failure Assessment score was associated with a reduced risk (per point, 0.89 [0.82-0.97]).ConclusionsIn ventilated stroke patients, decisions to limit life support are more than three times more frequent than in nonbrain-injured patients, with different timing and associated risk factors between ischemic and hemorrhagic strokes.
| S-EPMC7901798 | biostudies-literature
Project description:Rationale: Patients in the intensive care unit (ICU) are frequently exposed to unnecessary antibiotics. Markers of the host response to infection may aid pneumonia diagnosis and avoid antibiotic-induced complications. Objective: To assess the host response to suspected bacterial pneumonia through assessment of alveolar neutrophilia and transcriptomic profiling of alveolar macrophages. Methods: We determined the test characteristics of BAL neutrophilia for the diagnosis of bacterial pneumonia in 3 cohorts of mechanically ventilated patients. In one cohort, we also isolated alveolar macrophages from BAL fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: BAL neutrophilia was highly sensitive for bacterial pneumonia in both the retrospective (N = 851) and validation cohorts (N = 76 and N = 79) with a negative predictive value of over 90% when BAL neutrophil percentage was less than 50%. A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to BAL neutrophilia. Conclusions: A BAL neutrophil percentage of less than 50% is highly sensitive for bacterial pneumonia. Informative transcriptomic signatures can be generated from BAL fluid obtained during routine clinical care in the ICU. The identification of novel host response biomarkers is a promising approach to aid the diagnosis and treatment of pneumonia.
2018-11-06 | GSE121871 | GEO
Project description:Regionalization has been proposed as a method to improve outcomes for medical patients receiving mechanical ventilation in the intensive care unit.To determine the number of patients who would be affected by regionalization and the potential mortality reduction under a regionalized system of care.We performed a retrospective cohort study with Monte Carlo simulation, using 2001 state discharge data from eight states representing 42% of the U.S. population. Adult medical patients undergoing invasive mechanical ventilation were identified. Patient location and hospital mortality rates were obtained from the discharge data; estimates of the relative risk reduction in hospital mortality for high-volume hospitals compared with low-volume hospitals were obtained from the published literature and applied to the cohort.Of 180,976 adult medical patients who underwent mechanical ventilation at 1,170 nonfederal hospitals, 83,050 (46%) received mechanical ventilation at 887 (76%) hospitals with low annual volumes (fewer than 275 patients per year). Using published risk estimates, approximately 4,720 lives per year (95% range, 2,522-6,744) could potentially be saved in the 8 states by routinely transferring patients from low- to high-volume hospitals, representing a number needed to treat of 15.7. The median distance that patients would need to travel to reach a high-volume hospital was 8.5 miles (interquartile range, 4.0-21.2 mi).Regionalization of intensive care could potentially improve survival for patients undergoing mechanical ventilation. Transfer distances are modest for most patients.
| S-EPMC2218846 | biostudies-other
Project description:Tracheostomy is frequently performed in patients with severe ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Little is known about readmission rates among stroke patients who undergo mechanical ventilation.We used previously validated International Classification of Diseases, Ninth Edition-Clinical Modification codes and data on all discharges from nonfederal acute care hospitals in 3 states. We compared readmission rates among mechanically ventilated patients with stroke who were discharged with or without a tracheostomy.Among 39,881 patients who underwent mechanical ventilation during the index stroke hospitalization and survived to discharge, 10,690 (26.8%; 95% confidence interval, 26.4%-27.2%) underwent tracheostomy. During a mean follow-up period of 3.4 (±2.0) years, the overall incidence rate of readmissions was 4.25 (95% confidence interval, 4.22-4.28) per 100 patients per 30 days. The rate of any readmissions within 30 days was 26.9% among patients with tracheostomy compared with 22.5% among those without a tracheostomy (absolute risk difference, 4.4%; 95% confidence interval, 3.5%-5.4%; P<0.001). After adjustment for potentially confounding variables, tracheostomy was associated with a slightly increased readmission rate (incidence rate ratio, 1.07; 95% confidence interval, 1.03-1.11).Approximately one quarter of mechanically ventilated patients with stroke who survive to discharge are readmitted to the hospital within 30 days. Readmission rates are significantly higher in patients with stroke who undergo tracheostomy, but the difference is not clinically meaningful. Thirty-day readmission rates among mechanically ventilated patients with stroke are similar to Medicare beneficiaries hospitalized with major medical diseases such as pneumonia.
| S-EPMC4589479 | biostudies-literature