Brian K. Gehlbach

Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients.

Objective:In critically ill patients receiving mechanical ventilation, daily interruption of sedative infusions decreases duration of mechanical ventilation and intensive care unit length of stay. Whether this sedation strategy reduces the incidence of complications commonly associated with critical illness is not known. Design:Blinded, retrospective chart review. Setting:University-based hospital in Chicago, IL. Patients:One hundred twenty-eight patients receiving mechanical ventilation and continuous infusions of sedative drugs in a medical intensive care unit. Interventions:None. Measurements and Main Results:We performed a blinded, retrospective evaluation of the database from our previous trial of 128 patients randomized to daily interruption of sedative infusions vs. sedation as directed by the medical intensive care unit team without this strategy. Seven distinct complications associated with mechanical ventilation and critical illness were identified: a) ventilator-associated pneumonia; b) upper gastrointestinal hemorrhage; c) bacteremia; d) barotrauma; e) venous thromboembolic disease; and f) cholestasis or g) sinusitis requiring surgical intervention. The incidence of complications was evaluated for each patient’s hospital course.One hundred twenty-six of 128 charts were available for review. Patients undergoing daily interruption of sedative infusions experienced 13 complications (2.8%) vs. 26 (6.2%) in those subjected to conventional sedation techniques (p = .04). Conclusions:Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation reduces intensive care unit length of stay and, in turn, decreases the incidence of complications of critical illness associated with prolonged intubation and mechanical ventilation.

Daily sedative interruption in mechanically ventilated patients at risk for coronary artery disease.

Objectives:To determine the prevalence of myocardial ischemia in mechanically ventilated patients with coronary risk factors and compare periods of sedative interruption vs. sedative infusion. Design:Prospective, blinded observational study. Setting:Medical intensive care unit of tertiary care medical center. Patients:Intubated, mechanically ventilated patients with established coronary artery disease risk factors. Interventions:Continuous three-lead Holter monitors with ST-segment analysis by a blinded cardiologist were used to detect myocardial ischemia. Ischemia was defined as ST-segment elevation or depression of >0.1 mV from baseline. Measurements and Main Results:Comparisons between periods of awakening from sedation vs. sedative infusion were made. Vital signs, catecholamine levels, and time with ischemia detected by Holter monitor during the two periods were compared. Heart rate, mean arterial pressure, rate–pressure product, respiratory rate, and catecholamine levels were all significantly higher during sedative interruption. Eighteen of 74 patients (24%) demonstrated ischemic changes. Patients with myocardial ischemia had a longer intensive care unit length of stay (17.4 ± 17.5 vs. 9.6 ± 6.7 days, p = .04). Despite changes in vital signs and catecholamine levels during sedative interruption, fraction of ischemic time did not differ between the time awake vs. time sedated [median [interquartile range] of 0% [0, 0] compared with 0% [0, 0] while they were sedated [p = .17]). The finding of similar fractions of ischemic time between awake and sedated states persisted with analysis of the subgroup of 18 patients with ischemia. Conclusions:Myocardial ischemia is common in critically ill mechanically ventilated patients with coronary artery disease risk factors. Daily sedative interruption is not associated with an increased occurrence of myocardial ischemia in these patients.

Sedation in the intensive care unit.

Although the administration of sedatives is a commonplace activity in the ICU, few guidelines are available to aid the clinician in this practice. The first principle of sedative administration is to define the specific problem requiring sedation and to rationally choose the drug and depth of sedation appropriate for the indication. Next, the clinician must recognize the diverse and often unpredictable effects of critical illness on drug pharmacokinetics and pharmacodynamics. Failure to recognize these effects may lead initially to inadequate sedation and subsequently to drug accumulation. Drug accumulation may result in prolonged encephalopathy and mechanical ventilation and may mask the development of neurologic or intra-abdominal complications. Daily interruption of continuous sedative infusions is a simple and effective way of addressing this problem. A glossary of sedative drugs commonly used in the ICU is included in this review.

Temporal Disorganization of Circadian Rhythmicity and Sleep-Wake Regulation in Mechanically Ventilated Patients Receiving Continuous Intravenous Sedation

OBJECTIVES Sleep is regulated by circadian and homeostatic processes and is highly organized temporally. Our study was designed to determine whether this organization is preserved in patients receiving mechanical ventilation (MV) and intravenous sedation. DESIGN Observational study. SETTING Academic medical intensive care unit. PATIENTS Critically ill patients receiving MV and intravenous sedation. METHODS Continuous polysomnography (PSG) was initiated an average of 2.0 (1.0, 3.0) days after ICU admission and continued ≥ 36 h or until the patient was extubated. Sleep staging and power spectral analysis were performed using standard approaches. We also calculated the electroencephalography spectral edge frequency 95% SEF₉₅, a parameter that is normally higher during wakefulness than during sleep. Circadian rhythmicity was assessed in 16 subjects through the measurement of aMT6s in urine samples collected hourly for 24-48 hours. Light intensity at the head of the bed was measured continuously. MEASUREMENTS AND RESULTS We analyzed 819.7 h of PSG recordings from 21 subjects. REM sleep was identified in only 2/21 subjects. Slow wave activity lacked the normal diurnal and ultradian periodicity and homeostatic decline found in healthy adults. In nearly all patients, SEF₉₅ was consistently low without evidence of diurnal rhythmicity (median 6.3 [5.3, 7.8] Hz, n = 18). A circadian rhythm of aMT6s excretion was present in most (13/16, 81.3%) patients, but only 4 subjects had normal timing. Comparison of the SEF₉₅ during the melatonin-based biological night and day revealed no difference between the 2 periods (P = 0.64). CONCLUSIONS The circadian rhythms and PSG of patients receiving mechanical ventilation and intravenous sedation exhibit pronounced temporal disorganization. The finding that most subjects exhibited preserved, but phase delayed, excretion of aMT6s suggests that the circadian pacemaker of such patients may be free-running.

Sleep in the Intensive Care Unit

Sleep is an important physiologic process, and lack of sleep is associated with a host of adverse outcomes. Basic and clinical research has documented the important role circadian rhythm plays in biologic function. Critical illness is a time of extreme vulnerability for patients, and the important role sleep may play in recovery for intensive care unit (ICU) patients is just beginning to be explored. This concise clinical review focuses on the current state of research examining sleep in critical illness. We discuss sleep and circadian rhythm abnormalities that occur in ICU patients and the challenges to measuring alterations in circadian rhythm in critical illness and review methods to measure sleep in the ICU, including polysomnography, actigraphy, and questionnaires. We discuss data on the impact of potentially modifiable disruptors to patient sleep, such as noise, light, and patient care activities, and report on potential methods to improve sleep in the setting of critical illness. Finally, we review the latest literature on sleep disturbances that persist or develop after critical illness.

Atypical Sleep in Ventilated Patients: Empirical Electroencephalography Findings and the Path Toward Revised ICU Sleep Scoring Criteria.

Objectives:Standard sleep scoring criteria may be unreliable when applied to critically ill patients. We sought to quantify typical and atypical polysomnographic findings in critically ill patients and to begin development and reliability testing of methodology to characterize the atypical polysomnographic tracings that confound standard sleep scoring criteria. Design:Prospective convenience sample. Setting:Two academic, tertiary care medical centers. Patients:Thirty-seven critically ill, mechanically ventilated, medical ICU patients. Interventions:None. Measurements and Main Results:Mechanically ventilated subjects were monitored by continuous polysomnography. After noting frequent atypical polysomnographic findings (i.e., lack of stage N2 markers, the presence of polymorphic delta, burst suppression, or isoelectric electroencephalography), attempts to use standard sleep scoring criteria alone were abandoned. Atypical polysomnographic findings were characterized and used to develop a modified scoring system. Polysomnographic data were scored manually via this revised scoring scheme. Of 37 medical ICU patients enrolled, 36 experienced atypical sleep, which accounted for 85% of all recorded data, with 5.1% normal sleep and 9.4% wake. Coupling observed patient arousal levels with polysomnographic characteristics revealed that standard polysomnographic staging criteria did not reliably determine the presence or absence of sleep. Rapid eye movement occurred in only five patients (14%). The revised scoring system incorporating frequently seen atypical characteristics yielded very high interrater reliability (weighted &kgr; = 0.80; bootstrapped 95% CI, [0.48, 0.89]). Conclusions:Analysis of polysomnographic data revealed profound deficiencies in standard scoring criteria due to a predominance of atypical polysomnographic findings in ventilated patients. The revised scoring scheme proved reliable in sleep staging and may serve as a building block in future work.OBJECTIVES Standard sleep scoring criteria may be unreliable when applied to critically ill patients. We sought to quantify typical and atypical polysomnographic findings in critically ill patients and to begin development and reliability testing of methodology to characterize the atypical polysomnographic tracings that confound standard sleep scoring criteria. DESIGN Prospective convenience sample. SETTING Two academic, tertiary care medical centers. PATIENTS Thirty-seven critically ill, mechanically ventilated, medical ICU patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Mechanically ventilated subjects were monitored by continuous polysomnography. After noting frequent atypical polysomnographic findings (i.e., lack of stage N2 markers, the presence of polymorphic delta, burst suppression, or isoelectric electroencephalography), attempts to use standard sleep scoring criteria alone were abandoned. Atypical polysomnographic findings were characterized and used to develop a modified scoring system. Polysomnographic data were scored manually via this revised scoring scheme. Of 37 medical ICU patients enrolled, 36 experienced atypical sleep, which accounted for 85% of all recorded data, with 5.1% normal sleep and 9.4% wake. Coupling observed patient arousal levels with polysomnographic characteristics revealed that standard polysomnographic staging criteria did not reliably determine the presence or absence of sleep. Rapid eye movement occurred in only five patients (14%). The revised scoring system incorporating frequently seen atypical characteristics yielded very high interrater reliability (weighted κ = 0.80; bootstrapped 95% CI, [0.48, 0.89]). CONCLUSIONS Analysis of polysomnographic data revealed profound deficiencies in standard scoring criteria due to a predominance of atypical polysomnographic findings in ventilated patients. The revised scoring scheme proved reliable in sleep staging and may serve as a building block in future work.

Bench-to-bedside review: Treating acid–base abnormalities in the intensive care unit – the role of buffers

The recognition and management of acid–base disorders is a commonplace activity for intensivists. Despite the frequency with which non-bicarbonate-losing forms of metabolic acidosis such as lactic acidosis occurs in critically ill patients, treatment is controversial. This article describes the properties of several buffering agents and reviews the evidence for their clinical efficacy. The evidence supporting and refuting attempts to correct arterial pH through the administration of currently available buffers is presented.

Diagnostic utility of B-type natriuretic peptide in critically ill patients with pulmonary edema: a prospective cohort study

IntroductionDistinguishing pulmonary edema due to acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) from hydrostatic or cardiogenic edema is challenging in critically ill patients. B-type natriuretic peptide (BNP) can effectively identify congestive heart failure in the emergency room setting but, despite increasing use, its diagnostic utility has not been validated in the intensive care unit (ICU).MethodsWe performed a prospective, blinded cohort study in the medical and surgical ICUs at the University of Chicago Hospitals. Patients were eligible if they were admitted to the ICU with respiratory distress, bilateral pulmonary edema and a central venous catheter suggesting either high-pressure (cardiogenic) or low-pressure (ALI/ARDS) pulmonary edema. BNP levels were measured within 48 hours of ICU admission and development of pulmonary edema and onward up to three consecutive days. All levels were drawn simultaneously with the measurement of right atrial or pulmonary artery wedge pressure. The etiology of pulmonary edema – cardiogenic or ALI/ARDS – was determined by three intensivists blinded to BNP levels.ResultsWe enrolled a total of 54 patients (33 with ALI/ARDS and 21 with cardiogenic edema). BNP levels were lower in patients with ALI/ARDS than in those with cardiogenic edema (496 ± 439 versus 747 ± 476 pg/ml, P = 0.05). At an accepted cutoff of 100 pg/ml, specificity for the diagnosis of ALI/ARDS was high (95.2%) but sensitivity was poor (27.3%). Cutoffs at higher BNP levels improved sensitivity at considerable cost to specificity. Invasive measures of filling pressures correlated poorly with initial BNP levels and subsequent day BNP values fluctuated unpredictably and without correlation with hemodynamic changes and net fluid balance.ConclusionBNP levels drawn within 48 hours of admission to the ICU do not reliably distinguish ALI/ARDS from cardiogenic edema, do not correlate with invasive hemodynamic measurements, and do not track predictably with changes in volume status on consecutive daily measurements.

Excessive tidal volume from breath stacking during lung-protective ventilation for acute lung injury

Rationale:Low tidal volume ventilation strategies for patients with respiratory failure from acute lung injury may lead to breath stacking and higher volumes than intended. Objective:To determine frequency, risk factors, and volume of stacked breaths during low tidal volume ventilation for acute lung injury. Design, Setting, and Patients:Prospective cohort study of mechanically ventilated patients with acute lung injury (enrolled from August 2006 through May 2007) treated with low tidal volume ventilation in a medical intensive care unit at an academic tertiary care hospital. Interventions:Patients were ventilated with low tidal volumes using the Acute Respiratory Distress Syndrome Network protocol for acute lung injury. Continuous flow-time and pressure-time waveforms were recorded. The frequency, risk factors, and volume of stacked breaths were determined. Sedation depth was monitored using Richmond agitation sedation scale. Measurements and Main Results:Twenty patients were enrolled and studied for a mean 3.3 ± 1.7 days. The median (interquartile range) Richmond agitation sedation scale was −4 (−5, −3). Inter-rater agreement for identifying stacked breaths was high (kappa 0.99, 95% confidence interval 0.98–0.99). Stacked breaths occurred at a mean 2.3 ± 3.5 per minute and resulted in median volumes of 10.1 (8.8–10.7) mL/kg predicted body weight, which was 1.62 (1.44–1.82) times the set tidal volume. Stacked breaths were significantly less common with higher set tidal volumes (relative risk 0.4 for 1 mL/kg predicted body weight increase in tidal volume, 95% confidence interval 0.23–0.90). Conclusion:Stacked breaths occur frequently in low tidal volume ventilation despite deep sedation and result in volumes substantially above the set tidal volume. Set tidal volume has a strong influence on frequency of stacked breaths.

Sudden unexpected death in epilepsy: Fatal post-ictal respiratory and arousal mechanisms ☆

Sudden unexplained death in epilepsy (SUDEP) is the cause of premature death of up to 17% of all patients with epilepsy and as many as 50% with chronic refractory epilepsy. However, SUDEP is not widely recognized to exist. The etiology of SUDEP remains unclear, but growing evidence points to peri-ictal respiratory, cardiac, or autonomic nervous system dysfunction. How seizures affect these systems remains uncertain. Here we focus on respiratory mechanisms believed to underlie SUDEP. We highlight clinical evidence that indicates peri-ictal hypoxemia occurs in a large percentage of patients due to central apnea, and identify the proposed anatomical regions of the brain governing these responses. In addition, we discuss animal models used to study peri-ictal respiratory depression. We highlight the role 5-HT neurons play in respiratory control, chemoreception, and arousal. Finally, we discuss the evidence that 5-HT deficits contribute to SUDEP and sudden infant death syndrome and the striking similarities between the two.