Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation

Sztrymf, Benjamin; Chevrel, Guillaume; Bertrand, Fabrice; Margetis, Dimitri; Hurel, Dominique; Ricard, Jean Damien; Dreyfuss, Didier

doi:10.1186/cc9015

Cited by 15 publications

(13 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This suggests that some aspects of daily practice like care of agitated patients or weaning from IV hypnotics remain to be captured by local procedures. Neuroleptics have been proposed as first-line drugs for controlling agitation, discomfort, and delirium [6] and ventilator dyssynchrony [8]. However, their sparing effect on hypnotic use requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…These alternatives include short-duration (e.g., 6-h duration) IV infusions of hypnotics [6], repeated IV boluses of hypnotics (with no continuous IV infusion) [7], or the use of nonhypnotic drugs, such as neuroleptics [6,8]. Increasingly the concept of light sedation has emerged, where (once discomfort, dyssynchrony, and agitation have been controlled) patient awakeness and cooperation are promoted, rather than deep alterations of consciousness.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sedation in French intensive care units: a survey of clinical practice

B¹,

Vincent²,

Plantefève³

et al. 2013

Ann. Intensive Care

View full text Add to dashboard Cite

BackgroundSedation is used frequently for patients in intensive care units who require mechanical ventilation, but oversedation is one of the main side effects. Different strategies have been proposed to prevent oversedation. The extent to which these strategies have been adopted by intensivists is unknown.MethodsWe developed a six-section questionnaire that covered the drugs used, modalities of drug administration, use of sedation scales and procedural pain scales, use of written local procedures, and targeted objectives of consciousness. In November 2011, the questionnaire was sent to 1,078 intensivists identified from the French ICU Society (SRLF) database.ResultsThe questionnaire was returned by 195 intensivists (response rate 18.1%), representing 135 of the 282 ICUs (47.8%) listed in the French ICU society (SRLF) database. The analysis showed that midazolam and sufentanil are the most frequently used hypnotics and opioids, respectively, administered in continuous intravenous (IV) infusions. IV boluses of hypnotics without subsequent continuous IV infusion are used occasionally (in <25% of patients) by 65% of intensivists. Anxiolytic benzodiazepines (e.g., clorazepam, alprazolam), hydroxyzine, and typical neuroleptics, via either an enteral or IV route, are used occasionally by two thirds of respondents. The existence of a written, local sedation management procedure in the ICU is reported by 55% of respondents, 54% of whom declare that they use it routinely. Written local sedation procedures mainly rely on titration of continuous IV hypnotics (90% of the sedation procedures); less frequently, sedation procedures describe alternative approaches to prevent oversedation, including daily interruption of continuous IV hypnotic infusion, hypnotic boluses with no subsequent continuous IV infusion, or the use of nonhypnotic drugs. Among the responding intensivists, 98% consider eye opening, either spontaneously or after light physical stimulation, a reasonable target consciousness level in patients with no severe respiratory failure or intracranial hypertension.ConclusionsDespite a low individual response rate, the respondents to our survey represent almost half of the ICUs in the French SRLF database. The presence of a written local sedation procedure, a cornerstone of preventing oversedation, is reported by only half of respondents; when present, it is used in for a limited number of patients. Sedation procedures mainly rely on titration of continuous IV hypnotics, but other strategies to limit oversedation also are included in sedation procedures. French intensivists no longer consider severely altered consciousness a sedation objective for most patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sedation in French intensive care units: a survey of clinical practice

B¹,

Vincent²,

Plantefève³

et al. 2013

Ann. Intensive Care

View full text Add to dashboard Cite

show abstract

“…Lesem and coworkers (2011) published a multicenter, randomized, placebo-controlled study of inhaled loxapine for rapid acute treatment of agitation in individuals with schizophrenia, with positive findings. In a 2012 study, loxapine was effective for agitation during weaning from mechanical ventilation in 19 critical care patients, without adverse events after 150 mg administration via nasogastric tube, in up to two administrations, 90 minutes apart (Sztrymf et al 2010).…”

Section: Hellings Et Almentioning

confidence: 99%

Loxapine Add-on for Adolescents and Adults with Autism Spectrum Disorders and Irritability

Hellings

Reed

Cain

et al. 2015

Journal of Child and Adolescent Psychopharmacology

View full text Add to dashboard Cite

Objectives: Our clinical experience with low dose loxapine (5-15 mg/day) suggests promising efficacy and safety for irritability in autism spectrum disorders (ASD). We studied low dose loxapine prospectively in adolescents and adults with ASD and irritability. Additionally, we measured loxapine and metabolite concentrations, and brain-derived neurotrophic factor (BDNF) as a biomarker of neuromodulation. Methods: We performed a 12 week open trial of add-on loxapine in subjects, ages 13-65 years, diagnosed with ASD, and Aberrant Behavior Checklist-Irritability (ABC-I) subscale scores >14. Loxapine was dosed flexibly up to 15 mg daily, starting with 5 mg on alternate days. From weeks 1 to 6, other psychoactive medications were tapered if possible; from weeks 6 to 12, all medication doses were held stable. The primary outcome was the Clinical Global Impressions-Improvement subscale (CGI-I), ratings of Much Improved or Very Much Improved. Secondary outcomes were the ABC-I, Repetitive Behavior Scale-Revised, and Schalock Quality of Life scale. Serum BDNF and loxapine and metabolite concentrations were assayed. BDNF rs6265 was genotyped. Results: Sixteen subjects were enrolled; 12 completed all visits. Median age was 18 years (range 13-39). Median final loxapine dose was 7.5 mg/day (2.5-15). All 14 subjects (100%) with data at week 12 were rated as Much Improved on CGI-I at 12 weeks. Mean change on ABC-I at 12 weeks was -31%, p = 0.01. Mean body mass index (BMI)-Z decreased between weeks 6 and 12, p = 0.03. Side effects were minimal, and prolactin elevation occurred in only one subject. BDNF concentrations measured in 11 subjects increased significantly ( p = 0.04). Subjects with AG genotype for BDNF rs6265 required a lower dose of loxapine at study end, but had similar behavioral and BDNF concentration changes as the GG genotype.Conclusions: Low dose loxapine shows promise as a repurposed drug for irritability in ASD. Loxapine effects on BDNF warrant further study.

show abstract

“…On the other hand, the beneficial effects of alpha-2 adrenergic agonists, such as clonidine 27 or dexmedetomidine 28 , as well as of loxapine 29 on resolution of agitation during weaning from mechanical ventilation of patients who failed conventional therapy, provide an indirect evidence of the neurological and emotional stress the patients face during this critical period.…”

Section: Emotional Distress During Weaningmentioning

confidence: 99%

Neurormonal and inflammatory responses during weaning trials from mechanical ventilation

Routsi¹,

Papas²,

Zakynthinos³

2013

OA Critical Care

View full text Add to dashboard Cite

IntroductionWeaning from mechanical ventilation is usually accomplished with spontaneous breathing trials. The discontinuation of mechanical ventilation and the resumption of spontaneous breathing may increase oxygen demands, and patients, mainly those with limited cardiorespiratory reserve, are subjected to pulmonary and cardiovascular stress. In addition, emotional distress due to agitation after interruption of sedative drugs, anxiety and other sources of discomfort potentially contributes to pulmonary and cardiovascular stress. There is evidence of metabolic and endocrine stress response expressed as an increase in oxygen consumption and plasma concentration of catecholamines and other hormones involved in the stress system activation, in patients during the weaning process from mechanical ventilation, especially during failing weaning attempts. Furthermore, extrapolating from both physical exercise and inspiratory resistive breathing data, there is evidence of immune response expressed as an increase of proinflammatory cytokine blood levels. The purpose of this review is to summarise the published information about neurormonal and inflammatory stress response during weaning from mechanical ventilation. Neurormonal and inflammatory responses during weaning trials from mechanical ventilationC Routsi*, V Papas, S Zakynthinos ConclusionThe stress response during weaning trials from mechanical ventilation has not been studied enough. Nevertheless, there is evidence that the process of weaning from mechanical ventilation incorporates hormonal, inflammatory and neuroendocrine responses, indicating that weaning might prove physically and psychologically stressful. Further studies should evaluate this stress response more thoroughly for better management of these patients.

show abstract

Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation

Cited by 15 publications

References 32 publications

Sedation in French intensive care units: a survey of clinical practice

Sedation in French intensive care units: a survey of clinical practice

Loxapine Add-on for Adolescents and Adults with Autism Spectrum Disorders and Irritability

Neurormonal and inflammatory responses during weaning trials from mechanical ventilation

Contact Info

Product

Resources

About