Dataset Information

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation.

ABSTRACT:

Background

The 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.

Methods

This 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).

Results

The 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.

Conclusions

In patients mechanically ventilated for???96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.

SUBMITTER: Papazian L

PROVIDER: S-EPMC7876264 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation.

Papazian Laurent L Jaber Samir S Hraiech Sami S Baumstarck Karine K Cayot-Constantin Sophie S Aissaoui Nadia N Jung Boris B Leone Marc M Souweine Bertrand B Schwebel Carole C Bourenne Jérémy J Allardet-Servent Jérôme J Kamel Toufik T Lu Qin Q Zandotti Christine C Loundou Anderson A Penot-Ragon Christine C Chastre Jean J Forel Jean-Marie JM Luyt Charles-Edouard CE

Annals of intensive care 20210211 1

<h4>Background</h4>The 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.<h4>Methods</h4>This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in Fr ...[more]

PMID: 33570708

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Project description:ImportanceThe role of herpes simplex virus (HSV) reactivation on morbidity and mortality in patients in the intensive care unit requiring mechanical ventilation remains unknown.ObjectiveTo determine whether preemptive treatment with intravenous acyclovir reduces the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation.Design, setting, and participantsA 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.InterventionsParticipants were randomized to receive intravenous acyclovir, 5 mg/kg, 3 times daily for 14 days or a matching placebo.Main outcomes and measuresThe 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.ResultsOf 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 relevanceIn 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 registrationClinicalTrials.gov identifier: NCT02152358.

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.

Dataset Information

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation.

Background

Methods

Results

Conclusions

Publications

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation.

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