Delirium and Benzodiazepines Associated With Prolonged ICU Stay in Critically Ill Infants and Young Children*

Smith, Heidi; Gangopadhyay, Maalobeeka; Goben, Christina M.; Jacobowski, Natalie; Chestnut, Mary Hamilton; Thompson, Jennifer L.; Chandrasekhar, Rameela; Williams, Stacey; Griffith, Katherine; Ely, E. Wesley; Fuchs, Douglas; Pandharipande, Pratik P.

doi:10.1097/ccm.0000000000002515

Cited by 137 publications

(122 citation statements)

References 44 publications

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“…Sepsis is also a risk factor for ICU-acquired weakness and delirium [7][8][9]. Many of these hospital-acquired complications may contribute to a septic patient's prolonged ICU stay [10][11][12], increasing the chance of developing PCI. Thus, the development of PCI in patients with sepsis is of special interests.…”

Section: Introductionmentioning

confidence: 99%

Defining persistent critical illness based on growth trajectories in patients with sepsis

Zhang

et al. 2020

Crit Care

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Background: Persistent critical illness is common in critically ill patients and is associated with vast medical resource use and poor clinical outcomes. This study aimed to define when patients with sepsis would be stabilized and transitioned to persistent critical illness, and whether such transition time varies between latent classes of patients.Methods: This was a retrospective cohort study involving sepsis patients in the eICU Collaborative Research Database. Persistent critical illness was defined at the time when acute physiological characteristics were no longer more predictive of in-hospital mortality (i.e., vital status at hospital discharge) than antecedent characteristics. Latent growth mixture modeling was used to identify distinct trajectory classes by using Sequential Organ Failure Assessment score measured during intensive care unit stay as the outcome, and persistent critical illness transition time was explored in each latent class. Results: The mortality was 16.7% (3828/22,868) in the study cohort. Acute physiological model was no longer more predictive of in-hospital mortality than antecedent characteristics at 15 days after intensive care unit admission in the overall population. Only a minority of the study subjects (n = 643, 2.8%) developed persistent critical illness, but they accounted for 19% (15,834/83,125) and 10% (19,975/198,833) of the total intensive care unit and hospital beddays, respectively. Five latent classes were identified. Classes 1 and 2 showed increasing Sequential Organ Failure Assessment score over time and transition to persistent critical illness occurred at 16 and 27 days, respectively. The remaining classes showed a steady decline in Sequential Organ Failure Assessment scores and the transition to persistent critical illness occurred between 6 and 8 days. Elevated urea-to-creatinine ratio was a good biochemical signature of persistent critical illness. Conclusions: While persistent critical illness occurred in a minority of patients with sepsis, it consumed vast medical resources. The transition time differs substantially across latent classes, indicating that the allocation of medical resources should be tailored to different classes of patients.

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Section: Introductionmentioning

confidence: 99%

Defining persistent critical illness based on growth trajectories in patients with sepsis

Zhang

et al. 2020

Crit Care

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“…As DS patients have more complex recoveries than normal, it is entirely possible that any recovery lengthened by DS complications will require more sedatives that, in turn, will increase withdrawal symptoms after prolonged usage. Furthermore, a recent study showed that MDZ usage is a risk factor for developing pediatric delirium 38 . Taken together, these results pair well with our results and indicate that a new approach to sedation in DS patients is required.…”

Section: Discussionmentioning

confidence: 99%

Down Syndrome Reduces the Sedative Effect of Midazolam in Pediatric Cardiovascular Surgical Patients

Matsuishi

Sakuramoto

Hoshino

et al. 2020

Sci Rep

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Down syndrome (DS) is frequently comorbid with congenital heart disease and has recently been shown to reduce the sedative effect of benzodiazepine (BDZ)-class anesthesia but this effect in a clinical setting has not been studied. Therefore, this study compared midazolam sedation after heart surgery in DS and normal children. We retrospectively reviewed patient records in our pediatric intensive care unit (PICU) of pediatric cardiovascular operations between March 2015 and March 2018. We selected five days of continuous post-operative data just after termination of muscle relaxants. Midazolam sedation was estimated by Bayesian inference for generalized linear mixed models. We enrolled 104 patients (average age 26 weeks) of which 16 (15%) had DS. DS patients had a high probability of receiving a higher midazolam dosage and dexmedetomidine dosage over the study period (probability = 0.99, probability = 0.97) while depth of sedation was not different in DS patients (probability = 0.35). Multi regression modeling included severity scores and demographic data showed DS decreases midazolam sedation compared with controls (posterior OR = 1.32, 95% CrI = 1.01-1.75). In conclusion, midazolam dosages should be carefully adjusted as DS significantly decreases midazolam sedative effect in pediatric heart surgery patients.Down syndrome (DS), or trisomy 21, is the most common chromosome disorder 1 with a birth prevalence estimated at 1.5 per 1,000 2 and approximately 5,000 children are born with DS in the United States each year 3 . Similarly, a previous regional survey of Japan reported a prevalence of 1.5 per 1,000 live births 4 . Patients with DS frequently have associated developmental disorders and about 40% of children with DS are born with congenital heart disease (CHD) 5 , leading to higher mortality rates. Although many of these malformations can be surgically corrected, DS patients face additional risks such as airway obstruction while under sedation 6 . Recently, pharmacological interactions of dexmedetomidine (DEX), a highly selectiveα2-adrenergic agonist, with DS patients were shown to result in more side effects 7 . Additionally, benzodiazepine (BDZ), which increases GABA A receptor-mediated chloride ion influx, is thought to engender pharmaco-resistance in DS patients due to altered GABAergic transmission in area CA1 8 as seen in murine models. The manifestation of this effect has been clinically seen in case reports showing resistance to BDZ-class anesthesia midazolam (MDZ) in DS patients, such as dental surgery in a 35-year-old DS patient that required 3.5 mg MDZ before local anesthesia 9 . However, statistical confirmation of this effect in DS patients remains elusive 10 . Therefore, this study was conducted under the hypothesis that MDZ sedative effect is lessened in DS patients and aimed to use a sufficient sample size to discover the impact of MDZ resistance in pediatric surgery.

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“…10 No such evidence yet exists in PICU cohorts; some PICU studies demonstrate an association between delirium and infection, [11][12][13] and others do not. [14][15][16] Anticholinergic medications have been associated with increased risk of delirium in several PICU cohorts. 13,16 Measures of anticholinergic medication burden have been used extensively in the adult literature, and have been associated with quantitative measures of anticholinergic activity such as the SAA.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16] Anticholinergic medications have been associated with increased risk of delirium in several PICU cohorts. 13,16 Measures of anticholinergic medication burden have been used extensively in the adult literature, and have been associated with quantitative measures of anticholinergic activity such as the SAA. 17 One of the most commonly used scores is the anticholinergic drug scale (ADS), which rates individual medications using a variety of characteristics, including any known anticholinergic properties from pharmacological receptor-binding studies, known anticholinergic adverse events, or consensus expert opinion.…”

Section: Introductionmentioning

confidence: 99%

Exposure to Anticholinergic Medications in Pediatric Severe Sepsis and Feasibility of Delirium Screening

Madden

Callif

2020

J Pediatr Intensive Care

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In sepsis, anticholinergic dysregulation may result in encephalopathy or delirium during severe illness, either as a result of central inflammation or because of exposure to medications with anticholinergic activity. In this retrospective study, we determined the magnitude of anticholinergic drug exposure in 75 children with severe sepsis. We found that exposure over the first 5 days was high—median (interquartile range) daily anticholinergic drug scale score 4 (2–5)—and associated with higher vasoactive scores and death. We conclude that anticholinergic drug exposure is significant in severe sepsis, which means it may be a modifiable factor that should be studied further.

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Delirium and Benzodiazepines Associated With Prolonged ICU Stay in Critically Ill Infants and Young Children*

Cited by 137 publications

References 44 publications

Defining persistent critical illness based on growth trajectories in patients with sepsis

Defining persistent critical illness based on growth trajectories in patients with sepsis

Down Syndrome Reduces the Sedative Effect of Midazolam in Pediatric Cardiovascular Surgical Patients

Exposure to Anticholinergic Medications in Pediatric Severe Sepsis and Feasibility of Delirium Screening

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