Erik Garpestad

Efficacy and safety of quetiapine in critically ill patients with delirium: A prospective, multicenter, randomized, double-blind, placebo-controlled pilot study*

Objective: To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol. Design: Prospective, randomized, double-blind, placebo-controlled study. Setting: Three academic medical centers. Patients: Thirty-six adult intensive care unit patients with delirium (Intensive Care Delirium Screening Checklist score ≥4), tolerating enteral nutrition, and without a complicating neurologic condition. Interventions: Patients were randomized to receive quetiapine 50 mg every 12 hrs or placebo. Quetiapine was increased every 24 hrs (50 to 100 to 150 to 200 mg every 12 hrs) if more than one dose of haloperidol was given in the previous 24 hrs. Study drug was continued until the intensive care unit team discontinued it because of delirium resolution, therapy ≥10 days, or intensive care unit discharge. Measurements and Main Results: Baseline characteristics were similar between the quetiapine (n = 18) and placebo (n = 18) groups. Quetiapine was associated with a shorter time to first resolution of delirium [1.0 (interquartile range [IQR], 0.5–3.0) vs. 4.5 days (IQR, 2.0–7.0; p =.001)], a reduced duration of delirium [36 (IQR, 12–87) vs. 120 hrs (IQR, 60–195; p =.006)], and less agitation (Sedation-Agitation Scale score ≥5) [6 (IQR, 0–38) vs. 36 hrs (IQR, 11–66; p =.02)]. Whereas mortality (11% quetiapine vs. 17%) and intensive care unit length of stay (16 quetiapine vs. 16 days) were similar, subjects treated with quetiapine were more likely to be discharged home or to rehabilitation (89% quetiapine vs. 56%; p =.06). Subjects treated with quetiapine required fewer days of as-needed haloperidol [3 [(IQR, 2–4)] vs. 4 days (IQR, 3–8; p = .05)]. Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups, more somnolence was observed with quetiapine (22% vs. 11%; p = .66). Conclusions: Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation. Future studies should evaluate the effect of quetiapine on mortality, resource utilization, post-intensive care unit cognition, and dependency after discharge in a broader group of patients.

Noninvasive ventilation in acute respiratory failure.

Background:Noninvasive ventilation has assumed an important role in the management of respiratory failure in critical care units, but it must be used selectively depending on the patients diagnosis and clinical characteristics. Data:We review the strong evidence supporting the use of noninvasive ventilation for acute respiratory failure to prevent intubation in patients with chronic obstructive pulmonary disease exacerbations or acute cardiogenic pulmonary edema, and in immunocompromised patients, as well as to facilitate extubation in patients with chronic obstructive pulmonary disease who require initial intubation. Weaker evidence supports consideration of noninvasive ventilation for chronic obstructive pulmonary disease patients with postoperative or postextubation respiratory failure; patients with acute respiratory failure due to asthma exacerbations, pneumonia, acute lung injury, or acute respiratory distress syndrome; during bronchoscopy; or as a means of preoxygenation before intubation in critically ill patients with severe hypoxemia. Conclusion:Noninvasive ventilation has assumed an important role in managing patients with acute respiratory failure. Patients should be monitored closely for signs of noninvasive ventilation failure and promptly intubated before a crisis develops. The application of noninvasive ventilation by a trained and experienced intensive care unit team, with careful patient selection, should optimize patient outcomes.

MR imaging of pulmonary parenchyma with a half-Fourier single-shot turbo spin-echo (HASTE) sequence

OBJECTIVE To evaluate the utility of a half-Fourier single-shot turbo spin-echo sequence (HASTE) at depicting lung parenchyma and lung pathology. METHODS AND PATIENTS A HASTE sequence was applied to five normal volunteers and 20 patients with various pulmonary disorders to depict the lung parenchyma. Images were acquired with ECG-triggering and breath-holding. In three volunteers, signal intensity measurements from lung parenchyma were performed using four sequences: (a) HASTE; (b) conventional spin echo; (c) fast spin echo; and (d) gradient echo. T2 maps were produced using the HASTE acquisition. RESULTS Minimal respiratory or cardiac motion artifacts were observed. The signal-to-noise ratios from lung parenchyma were 27.8 +/- 5.4, 22.0 +/- 3.0, 15.3 +/- 0.9, and 6.0 +/- 1.9 for HASTE, spin-echo, fast spin-echo, and gradient echo sequences, respectively. The scan time for HASTE was 302 ms for each slice. The T2 values in the right lung and the left lung were 61.2 +/- 4.1 and 79.1 +/- 8.9 ms in systole and 92.6 +/- 5.8 and 97.5 +/- 12.2 ms in diastole, respectively (P < 0.05 diastole versus systole). The HASTE sequence demonstrated clearly various pulmonary disorders, including lung cancer, hilar lymphadenopathy, metastatic pulmonary nodules as small as 3 mm, pulmonary hemorrhage, pulmonary edema and bronchial wall thickening in bronchiectasis. CONCLUSION Our preliminary results indicate that the HASTE sequence provides a practical means for breath-hold MR imaging of lung parenchyma.

Use of a validated delirium assessment tool improves the ability of physicians to identify delirium in medical intensive care unit patients

Objective: Although medical intensive care unit nurses at our institution routinely use the Intensive Care Delirium Screening Checklist (ICDSC) to identify delirium, physicians rely on traditional diagnostic methods. We sought to measure the effect of physicians’ use of the ICDSC on their ability to detect delirium. Design: Before–after study. Setting: Medical intensive care unit of an academic medical center Patients and Participants: A total of 25 physicians with >=1 month of clinical experience in the medical intensive care unit conducted 300 delirium assessments in 100 medical intensive care unit patients. Measurements and Main Results: Physicians sequentially evaluated two patients for delirium using whatever diagnostic method preferred. Following standardized education regarding ICDSC use, each physician evaluated two different patients for delirium using the ICDSC. Each physician assessment was preceded by consecutive, but independent, evaluations for delirium by the patients nurse and then a validated judge using the ICDSC. Before (PRE) physician ICDSC use, the validated judge identified delirium in five patients; the physicians and nurses identified delirium in zero and four of these patients, respectively. The physicians incorrectly identified delirium in four additional patients. After (POST) physician ICDSC use, the validated judge identified delirium in 11 patients; the physicians and nurses identified delirium in eight and ten of these patients, respectively. The physicians incorrectly identified delirium in one patient. After physician ICDSC use, agreement improved between both the physicians and validated judge (PRE [kappa] = ‐0.14 [95% confidence interval {CI} = ‐0.27 to ‐0.02] to POST [kappa] = 0.67 [95% CI = 0.38 to 0.96]) and physicians and nurses (PRE [kappa] = ‐0.15 [95% CI = ‐0.29 to ‐0.02] to POST [kappa] = 0.58 [95% CI = 0.25 to 0.91]). Nurses vs. validated judge agreement was strong in both periods (PRE [kappa] = 0.65 [95% CI = 0.29 to 1.00] and POST [kappa] = 0.92 [95% CI = 0.76 to 1.00]). Conclusions: Use of the ICDSC, along with education supporting its use, improves the ability of physicians to detect delirium in the medical intensive care unit.

TGF-β1 Variants in Chronic Beryllium Disease and Sarcoidosis

Evidence suggests a genetic predisposition to chronic beryllium disease (CBD) and sarcoidosis, which are clinically and pathologically similar granulomatous lung diseases. TGF-β1, a cytokine involved in mediating the fibrotic/Th1 response, has several genetic variants which might predispose individuals to these lung diseases. We examined whether certain TGF-β1 variants and haplotypes are found at higher rates in CBD and sarcoidosis cases compared with controls and are associated with disease severity indicators for both diseases. Using DNA from sarcoidosis cases/controls from A Case Control Etiologic Study of Sarcoidosis Group (ACCESS) and CBD cases/controls, TGF-β1 variants were analyzed by sequence-specific primer PCR. No significant differences were found between cases and controls for either disease in the TGF-β1 variants or haplotypes. The −509C and codon 10T were significantly associated with disease severity indicators in both CBD and sarcoidosis. Haplotypes that included the −509C and codon 10T were also associated with more severe disease, whereas one or more copies of the haplotype containing the −509T and codon 10C was protective against severe disease for both sarcoidosis and CBD. These studies suggest that the −509C and codon 10T, implicated in lower levels of TGF-β1 protein production, are shared susceptibility factors associated with more severe granulomatous disease in sarcoidosis and CBD. This association may be due to lack of down-regulation by TGF-β1, although future studies will be needed to correlate TGF-β1 protein levels with known TGF-β1 genotypes and assess whether there is a shared mechanisms for TGF-β1 in these two granulomatous diseases.

Impact of quetiapine on resolution of individual delirium symptoms in critically ill patients with delirium: a post-hoc analysis of a double-blind, randomized, placebo-controlled study

IntroductionWe 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.MethodsData 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.ResultsBaseline 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].ConclusionsOur 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.

Impact of an Institution-Specific Hospital-Acquired Pneumonia Protocol on the Appropriateness of Antibiotic Therapy and Patient Outcomes

Study Objective. To evaluate the impact of a hospital‐acquired pneumonia (HAP) protocol on appropriateness of empiric antibiotic therapy, antibiotic deescalation, antibiotic duration, patient mortality, and length of stay.

Efficacy and Safety of Early Dexmedetomidine During Noninvasive Ventilation for Patients With Acute Respiratory Failure: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

BACKGROUND Successful application of noninvasive ventilation (NIV) for acute respiratory failure (ARF) requires patient cooperation and comfort. The efficacy and safety of early IV dexmedetomidine when added to protocolized, as-needed IV midazolam and fentanyl remain unclear. METHODS Adults with ARF and within 8 h of starting NIV were randomized to receive IV dexmedetomidine (0.2 μg/kg/h titrated every 30 min to 0.7 μg/kg/h to maintain a Sedation-Agitation Scale [SAS] score of 3 to 4) or placebo in a double-blind fashion up to 72 h, until NIV was stopped for ≥ 2 h, or until intubation. Patients with agitation (SAS ≥ 5) or pain (visual analog scale ≥ 5 of 10 cm) 15 min after each dexmedetomidine and placebo increase could receive IV midazolam 0.5 to 1.0 mg or IV fentanyl 25 to 50 μg, respectively, at a minimum interval of every 3 h. RESULTS The dexmedetomidine (n = 16) and placebo (n = 17) groups were similar at baseline. Use of early dexmedetomidine did not improve NIV tolerance (score, 1 of 4; OR, 1.44; 95% CI, 0.44-4.70; P = .54) nor, vs. placebo, led to a greater median (interquartile range) percent time either tolerating NIV (99% [61%-100%] vs. 67% [40%-100%], P = .56) or remaining at the desired sedation level (SAS score = 3 or 4, 100% [86%-100%] vs. 100% [100%-100%], P = .28], or fewer intubations (P = .79). Although use of dexmedetomidine was associated with a greater duration of NIV vs placebo (37 [16-72] vs. 12 [4-22] h, P = .03), the total ventilation duration (NIV + invasive) was similar (3.3 [2-4] days vs. 3.8 [2-5] days, P = .52). More patients receiving dexmedetomidine had one or more episodes of deep sedation vs placebo (SAS ≤ 2, 25% vs. 0%, P = .04). Use of midazolam (P = .40) and episodes of either severe bradycardia (heart rate ≤ 50 beats/min, P = .18) or hypotension (systolic BP ≤ 90 mm Hg, P = .64) were similar. CONCLUSIONS Initiating dexmedetomidine soon after NIV initiation in patients with ARF neither improves NIV tolerance nor helps to maintain sedation at a desired goal. Randomized, multicenter trials targeting patients with initial intolerance are needed to further elucidate the role for dexmedetomidine in this population.

Factors Influencing Variability in Compliance Rates and Clinical Outcomes Among Three Different Severe Sepsis Bundles

BACKGROUND: While 3 different quality indicator bundles are either approved (Voluntary Hospitals of America [VHA], Institute for Healthcare Improvement [IHI]) or proposed (Joint Commission on Accreditation of Healthcare Organizations [JCAHO]) to rate clinical practices in treatment of severe sepsis, it is suspected that differences in the quality indicators among these bundles may lead to discrepant benchmarking data. OBJECTIVE: To compare bundle compliance and patient factors associated with it among the IHI, JCAHO, and VHA severe sepsis bundles and explore possible reasons for any observed variability. METHODS: Using a retrospective, noninterventional design, we evaluated 50 adults (APACHE II score 25 ± 6, organ failure 2 ± 1, and shock 52%) with severe sepsis who were admitted consecutively to an intensive care unit at a 450 bed university-affiliated hospital. RESULTS: Few patients met 100% (IHI 6%, JCAHO 0%, VHA 6%) or 75% or greater (IHI 22%, JCAHO 6%, VHA 22%) of the quality indicators in each bundle. The number of patients who met 50% or more of the quality indicators varied significantly between JCAHO (28%) and both IHI (66%; p < 0.001) and VHA (60%; p < 0.001), but not between IHI and VHA (p = 0.53). Compliance with 50% or more of the quality indicators was more likely to occur when patients had shock (IHI, JCAHO, VHA), an APACHE II score greater than or equal to 25 (VHA), 2 or more organ failures (VHA), or survived hospitalization (IHI). We identified a number of factors that may help explain these differences. CONCLUSIONS: Differences among the IHI, JCAHO, and VHA severe sepsis bundles lead to variability in bundle compliance rates and the patient factors associated with the variability and may lead to confusion when benchmarking practices among institutions. Future efforts should focus on developing a single valid and reliable bundle that allows providers to improve the quality of sepsis care. TRANSFONDO: Tres diferentes organizaciones [“Voluntary Hospitals of America” (VHA), “Institute for Healthcare Improvement” (IHI), “Joint Commission on Accreditation of Healthcare Organizations” (JCAHO)] encargados con mejorar el cuidado médico en instituciones han desarrollado criterios de indicadores de calidad para el manejo apropiado de sepsis. Estas guiás de tratamiento han sido desarrollados con el propósito de proveer instituciones con un mecanismo para comparar la calidad de cuidado que ofrecen a sus pacientes que son admitidos con sepsis severa. Mientras que se han aprobado o propuesto tres diversos criterios de indicadores de calidad para evaluar las prácticas clínicas del manejo de sepsis severa, se sospecha que las diferencias entre estos indicadores pueden resultar en datos de comparación discrepantes.

Propofol Associated with a Shorter Duration of Mechanical Ventilation than Scheduled Intermittent Lorazepam: A Database Analysis Using Project IMPACT

Background: While one prospective controlled study in medical intensive care unit (ICU) patients demonstrated that sedation with propofol leads to a shorter duration of mechanical ventilation compared with scheduled intermittent intravenous lorazepam, its conclusions may not be applicable to surgical ICU patients and institutions not using daily sedation interruption. Objective: To compare the duration of mechanical ventilation between medical and surgical ICU patients receiving propofol versus scheduled intermittent lorazepam in routine clinical practice. Methods: Retrospective data (January 2001–December 2005) were obtained from the Project IMPACT database for medical and surgical ICU patients at Tufts-New England Medical Center, a 450 bed academic hospital. These patients had been mechanically ventilated for 24 hours or more and had received 24 hours or more of either propofol or scheduled intermittent lorazepam as the sole sedative. Clinically relevant variables were identified a priori, and their influence on duration of mechanical ventilation was evaluated. Differences in these variables between propofol and scheduled intermittent lorazepam groups within the ICU cohorts were then measured. Results: Of 4608 database patients, 287 met criteria. Factors associated with a prolonged duration of mechanical ventilation for the medical ICU cohort included sedation use for 5 or more days (OR 13.8; 95% CI 8.3 to 19.4), narcotic use (OR 7.6; 95% CI 2.3 to 13), and scheduled intermittent lorazepam use (OR 7.0; 95% CI 0.4 to 13.7). For the surgical ICU cohort, these factors included sedation use for 5 or more days (OR 15; 95% CI 11.4 to 19.4), APACHE II (Acute Physiology and Chronic Health Evaluation II) score equal to or greater than 18 (OR 4.1; 95% CI 0.4 to 7.8), and scheduled intermittent lorazepam use (OR 4.0; 95% CI 0.2 to 7.7). Duration of mechanical ventilation was the only variable that differed significantly between propofol and scheduled intermittent lorazepam in both the medical ICU, with a median (range) of 6 (3–12) versus 11 (5–25; p = 0.03), and surgical ICU, with a median of 4 (2–15) versus 9 (4–20; p = 0.001), groups. Conclusions: Sedation with propofol in the naturalistic setting appears to be associated with a shorter duration of mechanical ventilation compared with scheduled intermittent lorazepam in both medial and surgical ICU patients when only one sedative drug is used. Data from this uncontrolled observational study are consistent with findings from a randomized clinical trial.