An evaluation of instruments for scoring physiological and behavioral cues of pain,non-pain related distress,and adequacy of analgesia and sedation in pediatric mechanically ventilated patients: A systematic review

Objectives

Advancing technology allows for successful treatment of children with life-threatening illnesses. Effectively assessing and optimally treating a child's distress during their stay in the Pediatric Intensive Care Unit (PICU) is paramount. Objective measures of distress in mechanically ventilated pediatric patients are increasingly available but few have been evaluated. The objectives of this systematic review were to identify available instruments appropriate for measuring physiological and behavioral cues of pain, non-pain related distress, and adequacy of analgesia and sedation in mechanically ventilated pediatric patients, and evaluate these instruments in terms of their psychometric properties.

Design

A systematic review of original and validation reports of objective instruments to measure pain and non-pain related distress, and adequacy of analgesia and sedation in mechanically ventilated PICU patients was undertaken.

Data sources

A comprehensive search was conducted in 10 databases from January 1970 to June 2011. Reference lists of relevant articles were reviewed to identify additional articles.

Review methods

Studies were included in the review if they met pre-established eligibility criteria. Two independent reviewers reviewed studies for inclusion, assessed quality, and extracted data.

Results

Twenty-five articles were included, identifying 15 instruments. The instruments had different foci including: assessing pain, non-pain related distress, and sedation (n = 2); assessing pain exclusively (n = 4); assessing sedation exclusively (n = 7), assessing sedation in mechanically ventilated muscle relaxed PICU patients (n = 1); and assessing delirium in mechanically ventilated PICU patients (n = 1). The Comfort Scale demonstrated the greatest clinical utility in the assessment of pain, non-pain related distress, and sedation in mechanically ventilated pediatric patients. Modified FLACC and the MAPS are more appropriate, however, for the assessment of procedural pain and other brief painful events. More work is required on instruments for the assessment of distress in mechanically ventilated muscle relaxed PICU patients, and the assessment of delirium in PICU patients.

Conclusions

This review provides essential information to guide PICU clinicians in choosing instruments to assess pain, non-pain related distress, and adequacy of analgesia and sedation in mechanically ventilated pediatric patients. Effective knowledge translation is essential in the implementation, adoption, and successful use of these instruments.     

Comparison of CAM-ICU and ICDSC for the detection of delirium in critically ill patients focusing on relevant clinical outcomes

Purpose

Delirium is a frequent and serious problem in the intensive care unit (ICU) that is associated with increased mortality, prolonged mechanical ventilation, and prolonged hospital length of stay (LOS). The main objective of the present study was to compare and assess the agreement between the diagnosis of delirium obtained by the Confusion Assessment Method for the ICU (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) in patients admitted to the ICU and their association with outcomes.

Methods

Adult patients admitted to the ICU for more than 24 hours between May and November 2008 were included. Patients with a Richmond Agitation-Sedation Scale score of −4 to −5 for more than 3 days were excluded. Delirium was evaluated twice a day by the ICDSC and CAM-ICU. Patients were followed-up until ICU discharge or for a maximum of 28 days.

Results

During the study period, 383 patients were admitted to the ICU and 162 (42%) were evaluated; delirium was identified in 26.5% of patients by CAM-ICU and in 34.6% by ICDSC. There was agreement in diagnosing delirium diagnosis between the 2 methods in 42 (27.8%) patients and in excluding delirium in 105 (64.8%) patients. The ICDSC was positive in 14 (8.6%) patients in whom CAM-ICU was negative. Delirium, diagnosed either by ICDSC or CAM-ICU assessments, was associated with both significantly increased hospital LOS (14.8 ± 8.3 vs 9.8 ± 6.4, P < .001; 15.3 ± 8.7 vs 10.5 ± 7.1, P < .001, respectively), mortality in the ICU (11.1% vs 5.8%, P < .001; 12.5% vs 2.5%, P = .022), and in the hospital (10.7% vs 5.6%, P < .001; 23.2% vs 10.9%, P = .047). In addition, patients with positive ICDSC presenting with negative CAM-ICU had similar outcomes as compared with those without delirium.

Conclusion

The findings of our study suggest that the CAM-ICU is better predictor of outcome when compared with ICDSC.     

Predictors of mortality of mechanically ventilated patients in internal medicine wards

Purpose

Budget restrictions have led to shortage of intensive care unit (ICU) beds in several countries. Consequently, ventilated patients are often kept on the wards. This study examined survival likelihood among patients ventilated on the wards and the predictive value of commonly used severity-of-illness scores.

Methods

This study is a prospective observation and characterization of consecutive, mechanically ventilated patients in 3 internal medicine wards of a single hospital who were denied ICU admission. Outcome measures are as follows: 28-day mortality, survival to hospital discharge, and 3 months postdischarge.

Results

Eighty-six patients were examined. The patients were 78.9 ± 8.9 years old; 53% were independent preadmission. Respiratory insufficiency due to infection was the main reason for mechanical ventilation (58%). Charlson and acute physiology scores (APS) averaged 4 ± 2.2 and 91.8 ± 26.7, respectively. Twenty-eight-day mortality was 71%, whereas in-hospital mortality was 74% and 3 months postdischarge mortality was 79%. Survivors were significantly younger than nonsurvivors (74.4 ± 8.5 years vs 80.4 ± 8.6 years, P < .01), were more likely to be ventilated for cardiac causes (41% vs 11%, P = .04), and had significantly higher initial mean blood pressure (79.4 mm Hg vs 58.2 mm Hg, P = .02) and blood albumin levels (29.8 g/L vs 25.7 g/L, P = .05). Death rate was 10 times more likely, with an APS greater than 90 on the day of intubation as compared with an APS less than 90.

Conclusion

Mortality in patients ventilated on the ward was high, especially in the subgroup of patients with an APS score greater than 90. The early calculation of APS may assist in focusing therapeutic efforts on patients with better survival chances.     

Prediction of delirium in critically ill patients with elevated C-reactive protein

Background and Purpose

Delirium is thought to be associated with systemic inflammatory response. However, its association with the most widely used inflammatory biomarker C-reactive protein (CRP) has not been well established. We aimed to examine whether CRP on intensive care unit (ICU) entry was associated with subsequent development of delirium.

Design and Setting

This prospective observational study was conducted in a mixed 24-bed ICU in a tertiary teaching hospital.

Methods

All patients admitted to the ICU from February 2011 to June 2012 were screened for eligibility. Demographic data and clinical characteristics of included patients were recorded. Patients were screened for the presence of delirium by using the tool Confusion Assessment Method for the ICU (CAM-ICU). C-reactive protein was obtained on ICU entry and 24 hours thereafter. Eligible patients were followed up for 28 days or until death. Univariate and multivariate analyses were performed to evaluate independent risk factors for delirium. Clinical outcome included the length of stay (LOS) in the ICU, 28-day mortality, and duration of mechanical ventilation. Two-tailed P < .05 was considered statistically significant.

Results

A total of 223 patients were included during study period. In univariate analysis, patients with delirium showed significantly higher CRP values than those without (120.5 vs 57.5 mg/L; P = .0001). By adjusting for confounding variables (including age, sex, Acute Physiology and Chronic Health Evaluation II, intubation, living alone, physical restraint, alcohol drinking, smoking, type of medical condition, and hospital LOS before ICU admission) in logistic regression model, CRP remained an independent predictor of delirium (odds ratio, 1.07; 95% confidence interval, 1.01-1.15). As compared with nondelirious patients, those with delirium showed longer LOS in ICU (13 vs 5 days; P < .001) and duration of mechanical ventilation (6 vs 1 days; P < .001). An increase in CRP greater than 8.1 mg/L within 24 hours was associated with 4-fold increase in the risk of delirium (odds ratio: 4.47, 95% confidence interval, 1.28-15.60).

Conclusion

C-reactive protein measured on ICU entry and its changes within 24 hours are risk indicators of delirium. Further studies exploring the treatment of delirium according to CRP levels are warranted.     

The use of mechanical ventilation in the ED

Objectives

Although EDs are responsible for the initial care of critically ill patients and the amount of critical care provided in the ED is increasing, there are few data examining mechanical ventilation (MV) in the ED. In addition, characteristics of ED-based ventilation may affect planning for ventilator shortages during pandemic influenza or bioterrorist events. The study examined the epidemiology of MV in US EDs, including demographic, clinical, and hospital characteristics; indications for MV; ED length of stay (LOS); and in-hospital mortality.

Methods

This study was a retrospective review of the 1993 to 2007 National Hospital Ambulatory Medical Care Survey ED data sets. Ventilated patients were compared with ED patients admitted to the intensive care unit (ICU) and to all other ED visits.

Results

There were 3.6 million ED MV visits (95% confidence interval [CI], 3.2-4.0 million) over the study period. Sex, age, race, and payment source were similar for mechanically ventilated and ICU patients (P > .05 for all). Approximately 12.5% of ventilated patients underwent cardiopulmonary resuscitation compared with 1.7% of ICU admissions and 0.2% of all other ED visits (P < .0001). Accordingly, in-hospital mortality was significantly higher for ventilated patients (24%; 95% CI, 13.1%-34.9%) than both comparison groups (9.3% and 2.5%, respectively). Median LOS for ventilated patients was 197 minutes (interquartile range, 112-313 minutes) compared with 224 minutes for ICU admissions and 140 minutes for all other ED visits.

Conclusions

Patients undergoing ED MV have particularly high in-hospital mortality rates, but their ED LOS is sufficient for implementation of evidence-based ventilator interventions.     

Nurse-driven,protocol-directed weaning from mechanical ventilation improves clinical outcomes and is well accepted by intensive care unit physicians

Purpose

Ventilator weaning protocols can improve clinical outcomes, but their impact may vary depending on intensive care unit (ICU) structure, staffing, and acceptability by ICU physicians. This study was undertaken to examine their relationship.

Design/Methods

We prospectively examined outcomes of 102 mechanically ventilated patients for more than 24 hours and weaned using nurse-driven protocol-directed approach (nurse-driven group) in an intensivist-led ICU with low respiratory therapist staffing and compared them with a historic control of 100 patients who received conventional physician-driven weaning (physician-driven group). We administered a survey to assess ICU physicians' attitude.

Results

Median durations of mechanical ventilation (MV) in the nurse-driven and physician-driven groups were 2 and 4 days, respectively (P = .001). Median durations of ICU length of stay (LOS) in the nurse-driven and physician-driven groups were 5 and 7 days, respectively (P = .01). Time of extubation was 2 hours and 13 minutes earlier in the nurse-driven group (P < .001). There was no difference in hospital LOS, hospital mortality, rates of ventilator-associated pneumonia, or reintubation rates between the 2 groups. We identified 4 independent predictors of weaning duration: nurse-driven weaning, Acute Physiology and Chronic Health Evaluation II score, vasoactive medications use, and blood transfusion. Intensive care unit physicians viewed this protocol implementation positively (mean scores, 1.59-1.87 on a 5-point Likert scale).

Conclusions

A protocol for liberation from MV driven by ICU nurses decreased the duration of MV and ICU LOS in mechanically ventilated patients for more than 24 hours without adverse effects and was well accepted by ICU physicians.     

Validity and Reliability of the CAM-ICU Flowsheet to diagnose delirium in surgical ICU patients

Purpose

Delirium occurs frequently in critical care but often remains undiagnosed because delirium monitoring is often dismissed as being too time-consuming. This study determined the validity and reliability of the “CAM-ICU Flowsheet,” a practical, time-sparing algorithm to assess the 4 delirium criteria in intubated patients.

Materials and Methods

With permission from our institution's ethics committee, patients of a 31-bed surgical intensive care unit department were screened for delirium (1) by a psychiatrist as the reference rater using the 4 delirium criteria of the Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition (DSM-IV), and (2) by 2 physician investigators using a German translation of the CAM-ICU Flowsheet.

Results

Fifty-four surgical ICU patients underwent the complete protocol assessment with paired observations; 46% were diagnosed with delirium by the reference rater (n = 25), 9% had hyperactive delirium (n = 5), and 37% were hypoactive (n = 20). The CAM-ICU Flowsheet investigators had sensitivities of 88% (95% confidence interval, 69%-98%) and 92% (74%-99%), specificities of 100% (85%-100%), very high interrater reliability (κ, 0.96; 0.87-1.00), and needed 50 seconds (interquartile range, 40-120 seconds) in patients with delirium vs 45 seconds (interquartile range, 40–75 seconds) in those without delirium to complete assessments.

Conclusions

The CAM-ICU Flowsheet has high sensitivity, high specificity, and very high interrater reliability. False-negative ratings can occur infrequently and mostly reflect the fluctuating course of delirium. The CAM-ICU Flowsheet is a valid, reliable, and quickly performed bedside delirium instrument.     

Brain autopsy findings in intensive care unit patients previously suffering from delirium: A pilot study

Purpose

Delirium affects 50% to 80% of intensive care unit (ICU) patients and is associated with increased risk of mortality. Given the paucity of data reporting the neuropathologic findings in ICU patients experiencing delirium, the purpose of this pilot, hypothesis-generating study was to evaluate brain autopsies in ICU patients who suffered from delirium to explore possible neuroanatomical correlates.

Materials and Methods

Using delirium databases at Vanderbilt University, we identified patients who had delirium in the ICU and subsequently died and received a brain autopsy during the same hospitalization. Brain autopsy reports were collected retrospectively on all 7 patients who met these criteria.

Results

Patients' mean age was 55 (SD ± 8.4) years, and median number of days spent with delirium was 7 (±5 interquartile range). In 6 (86%) of 7 patients, pathologic lesions normally attributed to hypoxia or ischemia were noted in the hippocampus, pons, and striatum. Hippocampal lesions represented the most common neuropathologic site of injury, present in 5 (71%) of 7 patients.

Conclusions

Hypoxic ischemic injury in multiple locations of the brain was a common finding. The biological plausibility of hippocampal lesions as a contributor to long-term cognitive impairment warrants postmortem investigation on a larger scale with comparison to patients not experiencing ICU delirium.     

Implementation of a protocol for integrated management of pain,agitation, and delirium can improve clinical outcomes in the intensive care unit: A randomized clinical trial

Background

Inappropriate diagnosis and treatment of pain, agitation, and delirium (PAD) in intensive care settings results in poor patient outcomes. We designed and used a protocol for systematic assessment and management of PAD by the nurses to improve clinical intensive care unit (ICU) outcomes.

Materials and Methods

A total of 201 patients admitted to 2 mixed medical-surgical ICUs were randomly allocated to protocol and control groups. A multidisciplinary team approved the protocol. Pain was assessed by Numerical Rating Scale and Behavioural Pain Scale, agitation by Richmond Agitation Sedation Scale, and delirium by Confusion Assessment Method in ICU. The Persian version of the scales was prepared and tested for validity, reliability, and feasibility in a preliminary study. The patients in the protocol group were managed pharmacologically according to the protocol, whereas those in the control group were managed according to the ICU routine.

Results

The median (interquartile range) for the duration of mechanical ventilation in the protocol and control groups was 19 (9.3-67.8) and 40 (0-217) hours, respectively (P = .038). The median (interquartile range) length of ICU stay was 97 (54.5-189) hours in the protocol group vs 170 (80-408) hours in the control group (P < .001). The mortality rate in the protocol group was significantly reduced from 23.8% to 12.5% (P = .046).

Conclusion

The current randomized trial provided evidence for a substantial reduction in the duration of need to ventilatory support, length of ICU stay, and mortality rates in ICU-admitted patients through protocol-directed management of PAD.     

Delirium in patients admitted to a step-down unit: Analysis of incidence and risk factors

Background

Delirium is a rather common complication among patients admitted in intensive care units (ICUs), and rather than a single entity, it can be considered a spectrum of diseases where, besides overt cases, there are also many subsyndromal forms. Although there are many data about ICU delirium, there are few data concerning this complication in patients transferred from the ICU to a step-down unit (SDU) once clinically stable.

Objectives

With the present study, we wanted to assess the incidence of and risk factors for delirium and subsyndromal forms and their impact on clinical outcome in a group of patients transferred from an ICU to an SDU.

Methods

All patients transferred from an ICU to our SDU over a 2-year period were screened for delirium and subsyndromal delirious forms using the Intensive Care Delirium Screening Checklist, a simple tool already validated in the ICU. The following data were also recorded: demographic data, severity score (SAPS II), reason for admission to the SDU, length of stay, death rate, use of sedatives, impact of delirium on weaning from mechanical ventilation (MV).

Results

Among the 234 patients, the incidence of delirium and subsyndromal forms was 7.6% and 20%, respectively. Subsyndromal forms diagnosed at admission represented a risk factor for the subsequent development of delirium (odds ratio [OR], P < .0001). A previous episode of brain failure during ICU stay and older age were risks factors for the development of subsyndromal forms, whereas not needing MV was a protective factor. Delirium significantly prolonged the stay in the SDU but did not influence survival and the process of weaning from MV. Overall, the percentage of patients with an abnormal Intensive Care Delirium Screening Checklist score at discharge (5%) was reduced compared with that recorded at admission (18%).

Conclusions

Delirium may still occur after discharge from an ICU in patients who are transferred to an SDU. The strategy of care adopted in the SDU seems to positively affect the recovery from a delirious state. Patients with subsyndromal forms should be promptly recognized and treated because of the risk of developing delirium. Weaning from MV is not hindered by delirium.     

Rehabilitation therapy and outcomes in acute respiratory failure: An observational pilot project

Purpose

The aim of this study was to describe the frequency, physiologic effects, safety, and patient outcomes associated with traditional rehabilitation therapy in patients who require mechanical ventilation.

Materials and Methods

Prospective observational report of consecutive patients ventilated 4 or more days and eligible for rehabilitation in a single medical intensive care unit (ICU) during a 13-week period was conducted.

Results

Of the 32 patients who met the inclusion criteria, only 21 (66%) received physician orders for evaluation by rehabilitation services (physical and/or occupational therapy). Fifty rehabilitation treatments were provided to 19 patients on a median of 12% of medical ICU days per patient, with deep sedation and unavailability of rehabilitation staff representing major barriers to treatment. Physiologic changes during rehabilitation therapy were minimal. Joint contractures were frequent in the lower extremities and did not improve during hospitalization. In 53% and 79% of initial ICU assessments, muscle weakness was present in upper and lower extremities, respectively, with a decreased prevalence of 19% and 43% at hospital discharge, respectively. New impairments in physical function were common at hospital discharge.

Conclusions

This pilot project illustrated important barriers to providing rehabilitation to mechanically ventilated patients in an ICU and impairments in strength, range of motion, and functional outcomes at hospital discharge.     

Plethysmographic variation index predicts fluid responsiveness in ventilated patients in the early phase of septic shock in the emergency department: A pilot study

Purpose

Feasibility study examining whether plethysmographic variability index (PVI) can predict fluid responsiveness in mechanically ventilated patients in the early phase of septic shock in the emergency department.

Materials and Methods

Monocentric, prospective, observational study that included 31 mechanically ventilated and sedated patients with septic shock in whom volume expansion was planned. The patients were equipped with a pulse oximeter that automatically calculated and displayed PVI. The intervention consisted in infusing 8 mL/kg of hydroxylethyl starch over a 20-minute period. Before and after intervention, we recorded PVI and measured the aortic velocity-time integral (VTIao) using transthoracic echocardiography. Responders were defined as patients who increased their VTIao by 15% or higher after fluid infusion.

Results

Sixteen patients were classified as responders, and 15 as nonresponders. Mean PVI values before intervention were significantly higher in responders vs nonresponders (30% ± 9% vs 8% ± 5%, P < .001). Plethysmographic variability index values before intervention were correlated with percent changes in VTIao induced by intervention (R² = 0.67; P < .001). A PVI threshold value of 19% discriminates responders from nonresponders with a sensitivity of 94% and a specificity of 87% (area under the curve, 0.97; P < .001).

Conclusion

Our study suggests that PVI is a feasible and interesting method to predict fluid responsiveness in early phase septic shock patients in the emergency department.     

Observational study of patient-ventilator asynchrony and relationship to sedation level

Purpose

Clinicians frequently administer sedation to facilitate mechanical ventilation. The purpose of this study was to examine the relationship between sedation level and patient-ventilator asynchrony.

Materials and Methods

Airway pressure and airflow were recorded for 15 minutes. Patient-ventilator asynchrony was assessed by determining the number of breaths demonstrating ineffective triggering, double triggering, short cycling, and prolonged cycling. Ineffective triggering index (ITI) was calculated by dividing the number of ineffectively triggered breaths by the total number of breaths (triggered and ineffectively triggered). Sedation level was assessed by the following 3 methods: Richmond Agitation-Sedation Scale (RASS), awake (yes or no), and delirium (Confusion Assessment Method for the intensive care unit [CAM-ICU]).

Results

Twenty medical ICU patients underwent 35 observations. Ineffective triggering was seen in 17 of 20 patients and was the most frequent asynchrony (88% of all asynchronous breaths), being observed in 9% ± 12% of breaths. Deeper levels of sedation were associated with increasing ITI (awake, yes 2% vs no 11%; P < .05; CAM-ICU, coma [15%] vs delirium [5%] vs no delirium [2%]; P < .05; RASS, 0, 0% vs −5, 15%; P < .05). Diagnosis of chronic obstructive pulmonary disease, sedative type or dose, mechanical ventilation mode, and trigger method had no effect on ITI.

Conclusions

Asynchrony is common, and deeper sedation level is a predictor of ineffective triggering.     

Clearing up the confusion: The results of two pilot studies of antipsychotics for ICU delirium

Citation #1

Girard TD, Pandharipande PP, Carson SS, Schmidt GA, Wright PE, Canonico AE, Pun BT, Thompson JL, ShintaniAK, Meltzer HY, Bernard GR, Ditt us RS, Ely EW: Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med 2010, 38:428-437 [1].

Background

Given the lack of compelling evidence supporting the use of antipsychotics for delirium in critically ill patients and the potential adverse effects associated with these medications, placebo-controlled clinical trials are greatly needed.

Methods

Objective

To demonstrate the feasibility of a placebo-controlled trial of antipsychotics for delirium in the intensive care unit and to test the hypothesis that antipsychotics would improve days alive without delirium or coma.

Design

Randomized, double-blind, placebo-controlled trial.

Setting

Six tertiary care medical centers in the US.

Subjects

One hundred one mechanically ventilated medical and surgical intensive care unit patients.

Intervention

Patients were randomly assigned to receive haloperidol or ziprasidone or placebo every 6 hrs for up to 14 days. Twice each day, frequency of study drug administration was adjusted according to delirium status, level of sedation, and side effects.

Outcomes

The primary end point was the number of days patients were alive without delirium or coma. Secondary efficacy end points included daily delirium risk, duration of delirium, duration of coma, the number of days patients were alive and breathing without assistance during the 21-day study period (ventilator-free days), time to ICU and hospital discharge, and all-cause 21-day survival.

Results

During the 21-day study period, patients in the haloperidol group spent a similar number days alive without delirium or coma (median [inter quartile range], 14.0 [6.0-18.0] days) as did patients in the ziprasidone (15.0 [9.1-18.0] days) and placebo groups (12.5 [1.2-17.2] days; p = 0.66). No differences were found in secondary clinical outcomes, including ventilator-free days (p = .25), hospital length of stay (p = .68), and mortality (p = .81). Ten (29%) patients in the haloperidol group reported symptoms consistent with akathisia, compared with six (20%) patients in the ziprasidone group and seven (19%) patients in the placebo group (p = .60), and a global measure of extra pyramidal symptoms was similar between treatment groups (p = .46).

Conclusions

A randomized, placebo-controlled trial of antipsychotics for delirium in mechanically ventilated intensive care unit patients is feasible. Treatment with antipsychotics in this limited pilot trial did not improve the number of days alive without delirium or coma, nor did it increase adverse outcomes. Thus, a large trial is needed to determine whether use of antipsychotics for intensive care unit delirium is appropriate.

Citation #2

Devlin JW, Roberts RJ, Fong JJ, Skrobik Y, Riker RR, Hill NS, Robbins T, Garpestad E: Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multi center, randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010, 38:419-427 [2].

Background

To date, there are no published double-blind, randomized, placebo-controlled trials to establish the efficacy or safety of any antipsychotic medication in the management of delirium in the ICU.

Methods

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 in the US and Canada.

Subjects

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.

Intervention

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 m gevery 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.

Outcomes

The primary end point was time to first resolution of delirium. Secondary outcomes included duration of mechanical ventilation, ICU and hospital length of stay, hospital mortality, and discharge disposition. Measures of safety included total number of adverse and serious adverse events related to study drug, incidence of extra pyramidal symptoms, and episodes of QTc interval prolongation.

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 (inter quartile 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.     

Factors associated with persistent delirium after intensive care unit admission in an older medical patient population

Purpose

This study was designed to identify factors associated with persistent delirium in an older medical intensive care unit (ICU) population.

Materials and Methods

This is a prospective cohort study of 309 consecutive medical ICU patients 60 years or older. Persistent delirium was defined as delirium occurring in the ICU and continuing upon discharge to the ward. The Confusion Assessment Method was used to assess for delirium. Patient demographics, severity of illness, and medication data were collected. Univariate and multivariate analysis were used to assess factors associated with persistent delirium.

Results

Of 309 consecutive admissions to the ICU, 173 patients had ICU delirium, survived the ICU stay, and provided ward data. One-hundred patients (58%) had persistent delirium. In a multivariable logistic regression model, factors significantly associated with persistent delirium included age more than 75 years (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.23-5.16), opioid (morphine equivalent) dose greater than 54 mg/d (OR, 2.90; 95% CI, 1.15-7.28), and haloperidol (OR, 2.88; 95% CI, 1.38-6.02); change in code status to “do not resuscitate” (OR, 2.62; 95% CI 0.95-7.35) and dementia (OR, 1.93; 95% CI 0.95-3.93) had less precise associations.

Conclusions

Age, use of opioids, and haloperidol were associated with persistent delirium. Further research is needed regarding the use of haloperidol and opioids on persistent delirium.     

Health-care system distrust in the intensive care unit

Purpose

To examine the performance and properties of the Revised Health Care System Distrust Scale among surrogates in the intensive care unit (ICU).

Materials and Methods

Pilot, prospective cohort study of 50 surrogates of adult, mechanically ventilated patients surveyed on days 1, 3, and 7 of ICU admission.

Results

Responses on the Health Care System Distrust Scale on day 1 ranged from 9 to 34 (possible range 9-45, with higher scores indicating more distrust), with a mean and SD of 20.3 ± 6.9. Factor analysis demonstrated a 2-factor structure, corresponding to the domains of values and competence. Cronbach α for the overall scale was .83, for the competence subscale, .76, and for the values subscale, .74. Health-care system distrust was inversely correlated with trust in ICU physicians (Pearson coefficient −.63). When evaluated over the course of each patient's ICU stay, health-care system distrust ratings decreased by 0.31 per patient-day (95% CI 0.55-0.06, P = .015). Correlation between health-care system distrust and trust in ICU physicians decreased slightly over time.

Conclusions

Among surrogates in the ICU, the Health Care System Distrust Scale has high internal consistency and convergent validity. There was substantial variability in surrogates' trust in the health-care system.     

Effect of preadmission sunlight exposure on intensive care unit–acquired delirium: A multicenter study

Purpose

It is assumed that there is a relation between light exposure and delirium incidence. The aim of our study was to determine the effect of prehospital light exposure on the incidence of intensive care unit (ICU)–acquired delirium.

Materials and Methods

Data from 3 ICUs in the Netherlands were analyzed retrospectively. Delirium was assessed with the Confusion Assessment Method for the ICU. Daily light intensity data were obtained from meteorological stations in the vicinity of the 3 hospitals. The association between light intensity and delirium incidence was analyzed using logistic regression analysis adjusting for known covariates for delirium.

Results

Data of 3198 patients, aged (mean ± SD) 61.9 ± 15.3 years with Acute Physiology and Chronic Health Evaluation II score 16.4 ± 6.6 were analyzed. Delirium incidence was 31.2% and did not vary significantly throughout the year. Twenty-eight-day preadmission photoperiod was highest in spring and lowest in winter; however, no association between light exposure and delirium incidence was found (odds ratio, 1.00; 95% confidence interval, 0.99-1.00; P = 0.72). Furthermore, delirium was significantly associated with age, infection, use of sedatives, Acute Physiology and Chronic Health Evaluation II score, and diagnosis of neurological disease or trauma.

Conclusions

The incidence of delirium does not differ per season and prior sunlight exposure does not play a role of importance in the development of ICU-acquired delirium.     

Systemic and bronchoalveolar cytokines as predictors of in-hospital mortality in severe community-acquired pneumonia

Objectives

The aim of this study was to determine whether cytokine expression (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α), C-reactive protein, and endotoxins on the first day of intensive care unit (ICU) admission are associated with hospital mortality in severe community-acquired pneumonia (CAP).

Design

This was a prospective study with bronchoalveolar lavage (BAL) and blood sampling.

Setting

This study was carried out in a 44-bed medical ICU of a 1700-bed university hospital.

Patients

Participants included 112 mechanically ventilated patients with severe CAP.

Interventions

Serum and BAL fluid IL-1β, IL-6, IL-8, IL-10, TNF-α, C-reactive protein, and endotoxins on the first day of ICU admission were obtained.

Measurements and Main Results

The concentrations of TNF-α in BALF and IL-6, IL-8, IL-10, and TNF-α in serum were higher in nonsurvivors than in survivor patients with CAP. Of these 112 patients with severe CAP (39%), 44 developed acute respiratory distress syndrome (ARDS); these patients seemed to have higher serum IL-6, IL-8, and IL-10 levels than did the non-ARDS group. Furthermore, in the ARDS population, we found that the endotoxin levels in the BAL fluid were higher in the survival than in the nonsurvival group and BAL fluid concentrations of IL-6, IL-8, and IL-1β and sera levels of IL-6 and IL-10 were lower in the survival than in the nonsurvival group, and they were associated with a high negative predictive value.

Conclusions

Serum and BAL fluid levels of the studied cytokines on admission may provide valuable prognostic information for patients with severe CAP.     

Outcomes for critically ill patients with HIV and severe sepsis in the era of highly active antiretroviral therapy

Rationale

With the advent of highly active antiretroviral therapy (HAART), sepsis has become a more frequent ICU diagnosis for patients with HIV infections. Yet, little is known about the etiologies of acute infections in critically ill patients with HIV and the factors that affect in-hospital mortality.

Methods

Cases of patients with HIV requiring intensive care specifically for severe sepsis were identified over 27 months. Demographic information, variables related to acute illness severity, variables related to HIV infection, and all acute infections contributing to ICU stay were recorded.

Results

Of 990 patients admitted to the ICU with severe sepsis, 136 (13.7%) were HIV-infected. There were 194 acute infections among the 125 patients with full data available; 112 of the infections were nosocomial/health care–associated, 55 were AIDS-related, and 27 were community-acquired. Patients with nosocomial/health care–associated and AIDS-related infections had lower CD4 counts and were less likely to be on HAART (P < .05). The inpatient mortality was 42%. In a multivariable logistic regression model, only the APACHE II score (odds ratio, 1.12; 95% confidence interval, 1.02-1.23) was significantly associated with hospital mortality, although any HAART use (odds ratio, 0.53; 95% confidence interval, 0.22-1.33, P = .18) approached statistical significance.

Conclusions

In this large cohort study, nosocomial/health care–associated infections were common in ICU patients with HIV and severe sepsis. Hospital mortality was associated with acute illness severity, but not clearly associated with variables related to HIV infection. Interventions that aim to prevent or more effectively treat nosocomial infections in critically ill patients with HIV may favorably impact clinical outcomes.     

Previous antibiotic exposure and evolution of antibiotic resistance in mechanically ventilated patients with nosocomial infections

Purpose

This study aimed to evaluate the impact of previous antibiotic exposure and the influence of time interval since exposure on the evolution of antibiotic-resistant infections.

Methods

We retrospectively analyzed 167 mechanically ventilated patients with nosocomial infections over a 3-year period, with focus on infections in the bloodstream, urinary tract, lower respiratory tract, and surgical sites.

Results

Of 167 patients, 62% were confirmed as antibiotic resistant. The most common isolated pathogen was extended-spectrum β-lactamase Enterobacteriaceae (43.9%), followed by methicillin-resistant Staphylococcus aureus (22.8%), and carbapenem-resistant Acinetobacter baumannii (17.5%). Multivariate analysis revealed that the association between resistance and the time interval increased within 10 days (odds ratio [OR], 2.45; P = .133) and peaked at 11 to 20 days (OR, 7.17; P = .012). The data were categorized into 2 groups: when the time interval was more than 20 days, there was a 23.9% reduction in resistance rate compared with when the time interval was 20 days or less (OR, 0.36; P = .002).

Conclusions

Although antibiotic exposure increased resistance rate in nosocomial infections, this association decreased as time interval increased. Antibiotic stewardship should consider the significance of time interval while investigating the evolution of subsequent antibiotic-resistant infections.