quetiapine-fumarate and Critical-Illness

Practice guidelines provide clear evidence-based recommendations for the use of drug therapy to manage pain, agitation, and delirium associated with critical illness. Dosing recommendations however are often based on strategies used in patients with normal body habitus. Recommendations specific to critically ill patients with extreme obesity are lacking. Nonetheless, clinicians must craft dosing regimens for this population. This paper is intended to help clinicians design initial dosing regimens for medications commonly used in the management of pain, agitation, and delirium in critically ill patients with extreme obesity. A detailed literature search was conducted with an emphasis on obesity, pharmacokinetics, and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided.

Topics: Analgesia; Analgesics, Non-Narcotic; Analgesics, Opioid; Benzodiazepines; Critical Illness; Deep Sedation; Delirium; Dexmedetomidine; Dose-Response Relationship, Drug; Etomidate; Haloperidol; Humans; Ketamine; Obesity; Pain Management; Quetiapine Fumarate

The purpose of the study is to determine if pharmacologic approaches are effective in prevention and treatment of delirium in critically ill patients.. We performed a systematic search to identify publications (from January 1980 to September 2014) that evaluated the pharmacologic interventions to treat or prevent delirium in intensive care unit (ICU) patients.. From 2646 citations, 15 studies on prevention (6729 patients) and 7 studies on treatment (1784 patients) were selected and analyzed. Among studies that evaluated surgical patients, the pharmacologic interventions were associated with a reduction in delirium prevalence, ICU length of stay, and duration of mechanical ventilation, but with high heterogeneity (respectively, I(2) = 81%, P = .0013; I(2) = 97%, P < .001; and I(2) = 97%). Considering treatment studies, only 1 demonstrated a significant decrease in ICU length of stay using dexmedetomidine compared to haloperidol (Relative Risk, 0.62 [1.29-0.06]; I(2) = 97%), and only 1 found a shorter time to resolution of delirium using quetiapine (1.0 [confidence interval, 0.5-3.0] vs 4.5 [confidence interval, 2.0-7.0] days; P = .001).. The use of antipsychotics for surgical ICU patients and dexmedetomidine for mechanically ventilated patients as a preventive strategy may reduce the prevalence of delirium in the ICU. None of the studied agents that were used for delirium treatment improved major clinical outcome, including mortality.

Topics: Antipsychotic Agents; Critical Care; Critical Illness; Delirium; Dexmedetomidine; Haloperidol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypnotics and Sedatives; Intensive Care Units; Length of Stay; Neuroprotective Agents; Postoperative Complications; Quetiapine Fumarate; Respiration, Artificial; Risperidone; Rivastigmine; Treatment Outcome

Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population.. The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events.. The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002).. The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

Topics: Adult; Aged; Antipsychotic Agents; Chemoprevention; Critical Illness; Delirium; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Risk Assessment; Risk Factors; Trauma Severity Indices; Wounds and Injuries

We hypothesized that delirium symptoms may respond differently to antipsychotic therapy. The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the database of a randomized, double-blind, placebo-controlled study comparing quetiapine (Q) or placebo (P), both with haloperidol rescue, for critically ill patients with delirium.. Data for 10 delirium symptoms from the eight-domain, intensive care delirium screening checklist (ICDSC) previously collected every 12 hours were extracted for 29 study patients. Data between the Q and P groups were compared using a cut-off P-value of ≤ 0.10 for this exploratory study.. Baseline ICDSC scores (5 (4 to 7) (Q) vs 5 (4 to 6)) (median, interquartile range (IQR)) and % of patients with each ICDSC symptom were similar in the two groups (all P > 0.10). Among patients with the delirium symptom at baseline, use of Q may lead to a shorter time (days) to first resolution of symptom fluctuation (4 (Q) vs. 14, P = 0.004), inattention (3 vs. 8, P = .10) and disorientation (2 vs. 10, P = 0.10) but a longer time to first resolution of agitation (3 vs. 1, P = 0.04) and hyperactivity (5 vs. 1, P = 0.07). Among all patients, Q-treated patients tended to spend a smaller percent of time with inattention (47 (0 to 67) vs. 78 (43 to 100), P = 0.025), hallucinations (0 (0 to 17) vs. 28 (0 to 43), P = 0.10) and symptom fluctuation (47 (19 to 67) vs. 89 (33 to 00), P = 0.04] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness (26% (13 to 63%) vs. 14% (0 to 33%), P = 0.17].. Our exploratory analysis suggests that quetiapine may resolve several intensive care unit (ICU) delirium symptoms faster than the placebo. Individual symptom resolution appears to differ in association with the pharmacologic intervention (that is, P vs Q, both with as needed haloperidol). Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes.

Topics: Adult; Antipsychotic Agents; Critical Illness; Delirium; Dibenzothiazepines; Double-Blind Method; Haloperidol; Humans; Placebos; Quetiapine Fumarate; Retrospective Studies; Treatment Outcome

Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain.. The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine.. A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated.. This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias.. Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

Topics: Antipsychotic Agents; Arrhythmias, Cardiac; Child; Critical Illness; Delirium; Humans; Intensive Care Units; Quetiapine Fumarate; Retrospective Studies

The aim of this study was to evaluate quetiapine-associated pulmonary complications (PC) in critically injured trauma patients.. Injured adults admitted during 2016 to the ICU at a Level I trauma center were analyzed. Outcomes were evaluated by competing risks survival analysis.. Of 254 admissions, 40 (15.7%) had PC and 214 (84.3%) were non-events. PC patients were more severely injured, had longer hospital stays and were more likely to die. Patients administered quetiapine were more likely to develop PC and acquire PC earlier than those without quetiapine. Quetiapine was a positive risk factor for PC (sHR 2.24, p = 0.013). Stratification by ventilator use revealed non-ventilated patients administered quetiapine had the highest risk for PC (sHR 4.66, p = 0.099).. Quetiapine exposure in critically injured trauma patients was associated with increased risk of PC. Guidelines for treatment of delirium with quetiapine in critically injured trauma patients should account for this risk.

Topics: Antipsychotic Agents; Critical Illness; Delirium; Female; Humans; Intensive Care Units; Lung Diseases; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Trauma Centers; Wounds and Injuries

Quetiapine is an atypical antipsychotic commonly used in critical care. Cellular and animal models demonstrated its novel anti-inflammatory properties in traumatic brain injury (TBI). Our study aimed to assess the effect of quetiapine on outcomes in critically ill TBI patients. We hypothesize that quetiapine improves neurological outcomes.. The Multiparameter Intelligent Monitoring in Intensive Care database was queried, and all adult (age, ≥18 years) isolated TBI patients (extracranial Abbreviated Injury Scale, < 2) admitted to the intensive care unit for a period of >48 hours. Patients were stratified into quetiapine (+) and no-quetiapine (-) groups. Propensity score matching was performed (1:2 ratio). Outcome measures were intensive care unit length of stay, discharge Glasgow Coma Scale (GCS), and mortality. A subanalysis was performed for patients who underwent intracranial pressure (ICP) monitoring to ascertain the effect of quetiapine dose on ICP, and cerebral perfusion pressure (CPP). Survival curves and regression analyses were performed.. A matched cohort of (quetiapine, 116 vs. no-quetiapine, 232) patients was obtained. Mean ± SD age was 65 ± 21 years, median head Abbreviated Injury Scale was 3 (3-4), and median GCS was 10 (9-16). The median quetiapine dose given was 50 (25-125) mg. Patients who received quetiapine had lower mortality (17.2% vs. 27.6%; p = 0.03) and a higher median GCS at discharge (12 [11-14] vs. 11 [10-13]; p < 0.04) but no difference in intensive care unit length of stay (4.1 days vs. 4.7 days; p = 0.75) or discharge to skilled nursing facility (34.5% vs. 31.9%; p = 0.63). On subanalysis of patients who received quetiapine, 40% had ICP monitoring. Higher doses of quetiapine were independently associated with progressively lower ICP (β = -0.022 mm Hg/mg of quetiapine; p = 0.01) and higher CPP (β = 0.031 mm Hg/mg quetiapine; p = 0.01).. Quetiapine may decrease mortality and improve neurological outcomes in critically ill TBI patients. It has a dose-dependent effect to decrease ICP and increase CPP. Quetiapine may be a potential therapeutic modality in critically ill TBI patients, but further studies are required to explore these mechanisms.. Systematic Review, level III.

Topics: Adult; Aged; Aged, 80 and over; Brain Injuries, Traumatic; Cerebrovascular Circulation; Critical Illness; Female; Glasgow Coma Scale; Humans; Intensive Care Units; Intracranial Pressure; Length of Stay; Male; Massachusetts; Middle Aged; Monitoring, Physiologic; Neuroprotective Agents; Propensity Score; Quetiapine Fumarate; Retrospective Studies; Survival Analysis

Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Critical Illness; Humans; Neuroprotective Agents; Quetiapine Fumarate

Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Critical Illness; Humans; Neuroprotective Agents; Quetiapine Fumarate

To evaluate the efficacy and safety of lurasidone compared with quetiapine for treatment of delirium in critically ill patients.. Prospective, observational cohort study.. Single-center community teaching hospital.. Forty adult intensive care unit (ICU) patients with delirium (Confusion Assessment Method in the ICU positive), tolerating enteral nutrition, and without active alcohol withdrawal or prior use of atypical antipsychotics.. Patients were treated at the discretion of the prescriber with either lurasidone or quetiapine for delirium. Dose escalation and/or discontinuation were determined at the discretion of individual providers.. Baseline characteristics differed with a higher severity of illness in patients in the quetiapine group (n = 20) and a higher baseline QTc interval in the lurasidone group (n = 20). No significant difference was seen in the time to delirium resolution (3.2 vs 3.4 days), average daily haloperidol requirements (5.7 vs 6.9 mg), hospital length of stay (LOS; 23.6 vs 27.9 days), or ICU LOS (12.1 vs 14.2 days). Lurasidone was associated with fewer ventilator support days (4.0 [interquartile range, IQR: 2.3-6.8] days vs 7 [IQR: 4.0-9.8;. Lurasidone for the treatment of delirium in critically ill patients did not differ in the time to delirium resolution when compared to quetiapine. Additionally, the incidence of QTc prolongation between agents does not appear to be different. Future randomized trials should evaluate dose escalation schemes and a larger proportion of patients to evaluate differences in mortality, efficacy, and life-threatening arrhythmias associated with atypical antipsychotic use.

Topics: Aged; Antipsychotic Agents; Critical Care Outcomes; Critical Illness; Delirium; Female; Humans; Intensive Care Units; Lurasidone Hydrochloride; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

Topics: Antipsychotic Agents; Critical Illness; Delirium; Humans; Lurasidone Hydrochloride; Quetiapine Fumarate

Topics: Antipsychotic Agents; Critical Illness; Humans; Lurasidone Hydrochloride; Quetiapine Fumarate

Quetiapine is an atypical antipsychotic commonly utilized for the management of delirium in critically ill patients. The impact of quetiapine on QTc in the critically ill population is largely unknown.. The purpose of this study was to evaluate QTc prolongation following administration of quetiapine for the management of delirium in critically ill patients.. This was a single-center prospective, observational cohort study. QTc measurements of patients who received at least one dose of quetiapine were compared with a control group receiving melatonin. The primary outcome was mean change in QTc from baseline to maximum serum drug concentration after the first dose of quetiapine.. No significant change in QTc was observed from baseline to post-quetiapine administration, with a mean change in QTc of 2.7 ms (438.4 ± 43.2 ms vs 441.1 ± 36.4 ms; P = 0.50). When comparing mean change in QTc between the quetiapine group and melatonin group, the difference was not significant (2.7 ± 37.8 ms vs -0.18 ± 32.0 ms, P = 0.73). Conclusion and Relevance: This study represents one of the first prospective studies evaluating the impact of quetiapine on QTc. The results of this study demonstrate a nonsignificant statistical and clinical change in the QTc following quetiapine administration in critically ill patients utilizing telemetry measurements. Routine QTc monitoring with formal electrocardiogram(s) following quetiapine administration may not be warranted.

Topics: Adult; Antipsychotic Agents; Cohort Studies; Critical Illness; Delirium; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Telemetry

Quetiapine, an atypical antipsychotic used in the intensive care unit (ICU) to manage delirium, has a possible adverse effect of corrected QT (QTc) interval prolongation. The objective of this analysis was to describe the impact of quetiapine on QTc interval prolongation in critically ill patients. This was a single-center, prospective cohort analysis of ICU patients who received quetiapine between October 2015 and February 2016. The major end point was the incidence of QTc prolongation greater than 60 milliseconds above baseline during therapy. Minor end points included median change in QTc interval and incidence of Torsades de Pointes (TdP). Univariate and multivariable analyses were performed to determine variables associated with higher risk of QTc prolongation. During the study period, 103 patients were enrolled in the analysis. QTc interval prolongation greater than 60 milliseconds occurred in 14 (13.6%) patients. The median change in QTc interval was 20 milliseconds. There were no cases of TdP. On multivariable analysis, the only variable associated with higher incidence of QTc prolongation was administration of a concomitant medication known to prolong the QTc interval ( P = .046). QTc prolongation was relatively uncommon among critically ill patients utilizing quetiapine. Patients receiving concomitant medications known to prolong the QTc interval may be at an increased risk.

Topics: Aged; Antipsychotic Agents; Cohort Studies; Critical Illness; Delirium; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Treatment Outcome

Dosing regimens of quetiapine to treat delirium in critically ill patients are titrated to effect, and may utilize doses higher than previously reported. This study aimed to assess the safety of quetiapine for this indication.. A retrospective medical chart review was conducted, identifying 154 critically ill adults that were initiated on quetiapine to treat delirium and monitored for QTc prolongation.. The median average daily dose was 150 mg (79-234) and median max dose was 225 mg (100-350). The overall range was 25-800 mg daily. The time to peak dose was 3 days (1-8). Patients with QTc prolongation were significantly older (age 54 ± 11 vs 45 ± 17 years (p = 0.002)) and with higher baseline QTc (454 ± 33 vs 442 ± 30 (p = 0.045)). Regression analysis revealed only dose as a significant factor (OR = 1.006 (1.003-1.009) (p < 0.001)).. The dose of quetiapine has very little correlation with QTc and change from baseline. A small number of side effects were observed. Overall, titrating quickly to large doses of quetiapine is safe for treating delirium.

Topics: Adult; Aged; Antipsychotic Agents; Critical Care; Critical Illness; Delirium; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Risk Assessment

In this nationwide population-based study, we examined whether haloperidol exposure is associated with a higher risk of mortality than are other antipsychotic medications. Patients who newly received monotherapy with chlorpromazine (n = 2133), haloperidol (n = 4454), quetiapine (n = 1513), and risperidone (n = 1046) between January 1, 2001, and December 31, 2011, were selected from a random sample of the 1 million enrollees of the Taiwan National Health Insurance Research Database. The association between antipsychotic prescription and mortality was estimated through Cox proportional hazard regression. To examine the mortality rates of antipsychotics at different exposure durations, we compared the differences among short-term (≤30 days), midterm (31-90 days), and long-term (>90 days) antipsychotic use. The mortality rates during the follow-up among the chlorpromazine, haloperidol, quetiapine, and risperidone groups were 17.4%, 45.5%, 26.8%, and 25.9%, respectively. The mortality risk among patients receiving haloperidol was the highest within 30 days of the prescription, after which the risk reduced rapidly. Compared with the patients receiving chlorpromazine, the mortality risk was higher in short-term (adjusted hazard ratio, 2.11; 95% confidence interval, 1.87-2.39) and midterm haloperidol users (1.86; 1.54-2.25) than in long-term users (0.99; 0.61-1.61). In conclusion, haloperidol use is associated with higher mortality risk than other antipsychotic medications. The mortality risk varies according to the duration of drug exposure. Underlying characteristics and medical conditions may influence the estimation of the mortality risk. Clinicians should pay attention to the mortality risk when prescribing antipsychotic medications, particularly for the elderly and critically ill patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Chlorpromazine; Critical Illness; Female; Follow-Up Studies; Haloperidol; Humans; Male; Middle Aged; Mortality; Proportional Hazards Models; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Taiwan; Time Factors; Young Adult

Because delirium remains a common consequence of critical illness, and reducing its duration has been shown to have a positive impact on patient outcomes during and after an intensive care unit (ICU) stay, we sought to determine whether treatment of hypoactive delirium with quetiapine reduces the duration of delirium compared with no pharmacologic treatment.. Retrospective cohort study.. Three medical-surgical ICUs within the two main campuses of an academic tertiary care hospital system.. A total of 113 adults with documented hypoactive delirium during an ICU length of stay (LOS) of at least 72 hours between August 2013 and September 2014; 52 patients received at least one dose of quetiapine during their hypoactive delirium course, and 61 patients received no pharmacologic delirium treatment.. Patients were screened for hypoactive delirium using the Confusion Assessment Method-ICU (CAM-ICU) and the Richmond Agitation Sedation Scale (RASS). The primary outcome was time to first resolution of delirium, and secondary outcomes included ICU and hospital LOS, and duration of mechanical ventilation. To assess potential adverse effects of quetiapine, the number of RASS assessments deeper than goal and the total number of RASS assessments documented during the delirium course were recorded for all patients. Daily progress notes and discharge documentation were surveyed to assess for new onset of extrapyramidal symptoms or torsade de pointes. Median duration of hypoactive delirium was shorter in the quetiapine-treated group compared with the no-quetiapine group (1.5 vs 2.0 days, p=0.04), and time to extubation after screening positive for delirium trended favorably toward quetiapine-treated patients (3 vs 5 days, p=0.08). There were no significant differences in ICU or hospital LOS, and safety outcomes were similar between groups.. In this mixed ICU population, treatment of hypoactive delirium with quetiapine was safe and reduced the duration of delirium compared with standard care alone. Prospective placebo-controlled studies are needed to further assess the role of antipsychotics in hypoactive delirium.

Topics: Aged; Antipsychotic Agents; Critical Illness; Delirium; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies

Quetiapine is an atypical antipsychotic that has been used off-label for the treatment of intensive care unit (ICU) delirium in the adult population, with studies demonstrating both efficacy and a favorable safety profile. Although there is a potential role for quetiapine in the treatment of pediatric ICU delirium, there has been no systematic reporting to date of safety in this patient population.. Pharmacy records were used to identify 55 consecutive pediatric ICU patients who were diagnosed with delirium and received quetiapine. A comprehensive retrospective medical chart review was performed to collect data on demographics, dosing, and side effects.. Fifty patients treated between January 2013 and November 2014 were included, and five patients were excluded from the study. Subjects ranged in age from 2 months to 20 years. Median daily dose was 1.3 mg/kg/day, and median duration of treatment was 12 days. There were three episodes of QTc prolongation that were clinically nonsignificant with no associated dysrhythmia: Two resolved over time without intervention, and one resolved with decrease in quetiapine dosage. There were no episodes of extrapyramidal symptoms or neuroleptic malignant syndrome.. In this population of critically ill youth, short-term use of quetiapine as treatment for delirium appears to be safe, without serious adverse events. Further research is required to assess efficacy and evaluate for long-term effects. A prospective, randomized, placebo-controlled study of quetiapine in managing pediatric delirium is necessary.

Topics: Adolescent; Antipsychotic Agents; Child; Child, Preschool; Critical Illness; Delirium; Female; Humans; Infant; Male; Quetiapine Fumarate; Retrospective Studies; Young Adult