Allan Garland

Acquired Weakness, Handgrip Strength, and Mortality in Critically Ill Patients

RATIONALE ICU-acquired paresis (ICUAP) is common in survivors of critical illness. There is significant associated morbidity, including prolonged time on the ventilator and longer hospital stay. However, it is unclear whether ICUAP is independently associated with mortality, as sicker patients are more prone and existing studies have not adjusted for this. OBJECTIVES To test the hypothesis that ICUAP is independently associated with increased mortality. Secondarily, to determine if handgrip dynamometry is a concise measure of global strength and is independently associated with mortality. METHODS A prospective multicenter cohort study was conducted in intensive care units (ICU) of five academic medical centers. Adults requiring at least 5 days of mechanical ventilation without evidence of preexisting neuromuscular disease were followed until awakening and were then examined for strength. MEASUREMENTS AND MAIN RESULTS We measured global strength and handgrip dynamometry. The primary outcome was in-hospital mortality and secondary outcomes were hospital and ICU-free days, ICU readmission, and recurrent respiratory failure. Subjects with ICUAP (average MRC score of < 4) had longer hospital stays and required mechanical ventilation longer. Handgrip strength was lower in subjects with ICUAP and had good test performance for diagnosing ICUAP. After adjustment for severity of illness, ICUAP was independently associated with hospital mortality (odds ratio [OR], 7.8; 95% confidence interval [CI], 2.4-25.3; P = 0.001). Separately, handgrip strength was independently associated with hospital mortality (OR, 4.5; 95% CI, 1.5-13.6; P = 0.007). CONCLUSIONS ICUAP is independently associated with increased hospital mortality. Handgrip strength is also independently associated with poor hospital outcome and may serve as a simple test to identify ICUAP. Clinical trial registered with www.clinicaltrials.gov (NCT00106665).

Use of bispectral electroencephalogram monitoring to assess neurologic status in unsedated, critically ill patients

ObjectiveTo test whether spectral indices derived from the electroencephalogram (EEG), and especially the bispectral index (BIS), can be used as measures of neurologic status in unsedated, critically ill patients. DesignProspective, observational study. SettingMedical intensive care unit (ICU) of a university-affiliated teaching hospital. PatientsThirty-one awake, unsedated critically ill adults were assessed in 108 separate sessions. Measurements and Main Results In each session, severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE III). The APACHE III Acute Physiology Score was used to quantify the degree of physiologic derangement. Neurologic function was assessed using the APACHE III Neurologic Score, the Glasgow Coma Scale, the Reaction Level Scale, and the Modified Ramsay Sedation Scale. All indices were plotted against various spectral parameters of the EEG, including BIS, an empirical index of EEG activity that is scaled from 0 to 100. BIS was significantly (p < .05) correlated with neurologic score regardless of scoring system used and was more strongly correlated than any other EEG spectral parameter. Better neurologic function was associated with higher values of BIS. In multivariate analysis, the combination of BIS and relative power in the theta band of the EEG accounted for 38% of the variability in the Glasgow Coma Scale. ConclusionsBIS provides a reliable index of neurologic status in awake, unsedated, critically ill patients. Further research is needed to determine whether the effects of neurologic status and pharmacologic sedation upon EEG are additive, whether BIS can be used to assess pharmacologic sedation in the critically ill patient population, and whether such objective measures of neurologic status have prognostic value.

Quantile regression and restricted cubic splines are useful for exploring relationships between continuous variables

OBJECTIVE Ordinary least squares (OLS) regression, commonly called linear regression, is often used to assess, or adjust for, the relationship between a continuous independent variable and the mean of a continuous dependent variable, implicitly assuming a linear relationship between them. Linearity may not hold, however, and analyzing the mean of the dependent variable may not capture the full nature of such relationships. Our goal is to demonstrate how combined use of quantile regression and restricted cubic splines (RCS) can reveal the true nature and complexity of relationships between continuous variables. STUDY DESIGN AND SETTING We provide a review of methodologic concepts, followed by two examples using real data sets. In the first example, we analyzed the relationship between cognition and disease duration in multiple sclerosis. In the second example, we analyzed the relationship between length of stay (LOS) and severity of illness in the intensive care unit (ICU). RESULTS In both examples, quantile regression showed that the relationship between the variables of interest was heterogeneous. In the second example, RCS uncovered nonlinearity of the relationship between severity of illness and length of stay. CONCLUSION Together, quantile regression and RCS are a powerful combination for exploring relationships between continuous variables.

Effectiveness Trial of an Intensive Communication Structure for Families of Long-Stay ICU Patients

BACKGROUND Formal family meetings have been recommended as a useful approach to assist in goal setting, facilitate decision making, and reduce use of ineffective resources in the ICU. We examined patient outcomes before and after implementation of an intensive communication system (ICS) to test the effect of regular, structured formal family meetings on patient outcomes among long-stay ICU patients. METHODS One hundred thirty-five patients receiving usual care and communication were enrolled as the control group, followed by enrollment of intervention patients (n = 346), from five ICUs. The ICS included a family meeting within 5 days of ICU admission and weekly thereafter. Each meeting discussed medical update, values and preferences, and goals of care; treatment plan; and milestones for judging effectiveness of treatment. RESULTS Using multivariate analysis, there were no significant differences between control and intervention patients in length of stay (LOS), the primary end point. Similarly, there were no significant differences in indicators of aggressiveness of care or treatment limitation decisions (ICU mortality, LOS, duration of ventilation, treatment limitation orders, or use of tracheostomy or percutaneous gastrostomy). Exploratory analysis suggested that in the medical ICUs, the intervention was associated with a lower prevalence of tracheostomy among patients who died or had do-not-attempt-resuscitation orders in place. CONCLUSIONS The negative findings of the main analysis, in combination with preliminary evidence of differences among types of unit, suggest that further examination of the influence of patient, family, and unit characteristics on the effects of a system of regular family meetings may be warranted. Despite the lack of influence on patient outcomes, structured family meetings may be an effective approach to meeting information and support needs. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01057238 ; URL: www.clinicaltrials.gov.

Interaction between fluids and vasoactive agents on mortality in septic shock: a multicenter, observational study.

Objective:Fluids and vasoactive agents are both used to treat septic shock, but little is known about how they interact or the optimal way to administer them. We sought to determine how hospital mortality was influenced by combined use of these two treatments. Design:Retrospective evaluation using multivariable logistic regression to evaluate the association between hospital mortality and categorical variables representing initiation of vasoactive agents and volumes of IV fluids given 0–1, 1–6, and 6–24 hours after onset, including interactions and adjusting for potential confounders. Setting:ICUs of 24 hospitals in 3 countries. Patients:Two thousand eight hundred forty-nine patients who survived more than 24 hours after after onset of septic shock, admitted between 1989 and 2007. Interventions:None. Measurements and Main Results:Fluids and vasoactive agents had strong, interacting associations with mortality (p < 0.0001). Mortality was lowest when vasoactive agents were begun 1–6 hours after onset, with more than 1 L of fluids in the initial hour after shock onset, more than 2.4 L from hours 1–6, and 1.6–3.5 L from 6 to 24 hours. The lowest mortality rates were associated with starting vasoactive agents 1–6 hours after onset. Conclusions:The focus during the first hour of resuscitation for septic shock should be aggressive fluid administration, only thereafter starting vasoactive agents, while continuing aggressive fluid administration. Starting vasoactive agents in the initial hour may be detrimental, and not all of that association is due to less fluids being given with such early initiation of vasoactive agents.

Twenty-four-hour intensivist presence: a pilot study of effects on intensive care unit patients, families, doctors, and nurses.

RATIONALE Around-the-clock intensivist presence in intensive care units (ICUs) has been promoted as necessary to optimize outcomes. Little data have addressed how it affects the multiple stakeholders in such care. OBJECTIVES To assess effects of around-the-clock intensivist presence on intensivists, patients, families, housestaff, and nurses. METHODS This 32-week, crossover pilot trial of two intensivist staffing models, performed in two Canadian ICUs, alternated 8-week blocks of two staffing models: the standard model, where one intensivist worked for 7 days, taking night call from home; and the shift work model, where one intensivist worked 7 day shifts, while other intensivists remained in the ICU at night. MEASUREMENTS AND MAIN RESULTS Surveys scaled from 0-100 points assessed outcomes for 24 intensivists (primary outcome: burnout); 119 families (satisfaction); 74 nurses (satisfaction with collaboration and communications, role conflict); and 34 housestaff (autonomy, supervision, and learning opportunities). Outcomes for 501 patients included mortality, length of stay, and resource use. Intensivists doing shift work experienced less burnout (-6.9 points; P = 0.04). Adjusted hospital mortality (odds ratio, 1.22; P = 0.44), ICU length of stay (-6 h; P = 0.46), and family satisfaction (0.9 points; P = 0.79) did not differ between staffing models. Under shift work staffing, nurses reported more role conflict (9 points; P < 0.001), whereas nighttime housestaff reported less autonomy, more supervision, but no difference in learning opportunities. CONCLUSIONS Shiftwork staffing was better for intensivists and most were receptive once they had experienced it. Although there were no evident negative outcomes for patients or families, further evaluation is needed to clarify how around-the-clock intensivist staffing influences the various stakeholders in ICU care, given power considerations in this study. Clinical trial registered with www.clinicaltrials.gov (NCT 01146691).

Effect of clinical outcomes data on intensive care unit utilization by bone marrow transplant patients

OBJECTIVE To determine if a program to educate referring physicians as to the poor outcome of mechanically ventilated bone marrow transplant patients would result in a change in intensive care unit (ICU) utilization. DESIGN Retrospective chart review. SETTING Medical ICU at an urban university hospital. PATIENTS Patients undergoing bone marrow transplantation in the interval before (n = 236) vs. the interval after (n = 144) a physician education program. INTERVENTIONS Two separate educational programs were conducted for oncologists and intensivists to review the findings of an earlier study demonstrating the outcome of bone marrow transplant patients in the ICU. MEASUREMENTS AND MAIN RESULTS The results demonstrated that this physician education intervention did not result in a change in the utilization of medical ICU resources by these patients. Comparing the time periods before and after the intervention, there were no statistically significant differences in the proportion of patients who were admitted to the medical ICU, the proportion who received mechanical ventilation, or the medical ICU lengths of stay. Similarly, the two groups did not differ regarding the 100-day survival rate of all bone marrow transplant patients studied, all bone marrow transplant patients admitted to the medical ICU, or all bone marrow transplant patients intubated. CONCLUSION Simple educational interventions are not a powerful mechanism by which to alter the practice of physicians regarding the utilization of scarce and expensive resources, even when the physicians generally agree that the use of those resources results in dismal patient outcomes.

Tachykinin receptor antagonists inhibit hyperpnea-induced bronchoconstriction in guinea pigs.

We tested the hypothesis that hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH) are mediated through stimulation of NK-1 and NK-2 receptors in guinea pigs. We first established the efficacy and selectivity of (+/-) CP-96,345 (3 mg/kg i.v.) and of SR-48,968 (300 micrograms/kg i.v.) as NK-1 and NK-2 antagonists, respectively. (+/-) CP-96,345 substantially attenuated bronchoconstriction and systemic vascular leak caused by administration of Sar9,Met(O2)11-Substance P (a specific NK-1 agonist), but had no effect upon bronchoconstriction induced by selective NK-2 stimulation with Nle10-Neurokinin A[4-10]. Conversely, SR-48,968 antagonized the bronchoconstrictor response to Nle10-NKA[4-10], right-shifting the dose-response curve by 2 log units, but had no effect on Sar9, Met(O2)11-SP-induced bronchoconstriction. Anesthetized, tracheostomized, opened-chest male Hartley guinea pigs were pretreated with (+/-) CP-96,345 (3 mg/kg i.v.), SR-48,968 (300 micrograms/kg i.v.), or their respective vehicles, and Evans blue dye (30 mg/kg i.v.) to label circulating albumin. 10 min isocapnic dry gas hyperpnea (12 ml/kg, 150 breaths/min) provoked HIB and HIBVH in vehicle-treated animals. (+/-) CP-96,345 reduced the magnitude of HIB by one-half (peak posthyperpnea RL 7.8 +/- 1.9 [SE] times prehyperpnea baseline versus 16.1 +/- 2.6, vehicle-treated; P < or = 0.0001, ANOVA); SR-48,968 blocked HIB more completely (peak posthyperpnea RL 5.1 +/- 1.7 [SE] times prehyperpnea baseline versus 19.3 +/- 2.8, vehicle-treated; P < 0.0001, ANOVA). Neither drug reduced HIBVH. We conclude that dry gas hyperpnea causes bronchoconstriction in guinea pigs through activation of tachykinin receptors. The differential effects of neurokinin receptor blockade on HIB and HIBVH demonstrate that hyperpnea-induced airflow obstruction is not primarily a consequence of hyperpnea-induced bronchovascular leak.

Continuity of care in intensive care units: a cluster-randomized trial of intensivist staffing.

RATIONALE Little is known about the consequences of intensivists’ work schedules, or intensivist continuity of care. OBJECTIVES To assess the impact of weekend respite for intensivists, with consequent reduction in continuity of care, on them and their patients. METHODS In five medical intensive care units (ICUs) in four academic hospitals we performed a prospective, cluster-randomized, alternating trial of two intensivist staffing schedules. Daily coverage by a single intensivist in half-month rotations (continuous schedule) was compared with weekday coverage by a single intensivist, with weekend cross-coverage by colleagues (interrupted schedule). We studied consecutive patients admitted to study units, and the intensivists working in four of the participating units. MEASUREMENTS AND MAIN RESULTS The primary patient outcome was ICU length of stay (LOS);we also assessed hospital LOS and mortality rates. The primary intensivist outcome was physician burnout. Analysis was by multivariable regression. A total of 45 intensivists and 1,900 patients participated in the study. Continuity of care differed between schedules (patients with multiple intensivists = 28% under continuous schedule vs. 62% under interrupted scheduling; P < 0.0001). LOS and mortality were nonsignificantly higher under continuous scheduling (ΔICU LOS 0.36 d, P = 0.20; Δhospital LOS 0.34 d, P = 0.71; ICU mortality, odds ratio = 1.43, P = 0.12; hospital mortality, odds ratio = 1.17,P = 0.41). Intensivists experienced significantly higher burnout, work–home life imbalance, and job distress working under the continuous schedule. CONCLUSIONS Work schedules where intensivists received weekend breaks were better for the physicians and, despite lower continuity of intensivist care, did not worsen outcomes for medical ICU patients.

Hypertonicity, but not hypothermia, elicits substance P release from rat C-fiber neurons in primary culture.

Isocapnic dry gas hyperventilation provokes hyperpnea-induced bronchoconstriction in guinea pigs by releasing tachykinins from airway sensory C-fiber neurons. It is unknown whether dry gas hyperpnea directly stimulates C-fibers to release tachykinins, or whether this physical stimulus initiates a mediator cascade that indirectly stimulates C-fiber tachykinin release. We tested the hypotheses that mucosal hypothermia and/or hyperosmolarity--physical consequences of airway heat and water loss imposed by dry gas hyperpnea--can directly stimulate C-fiber tachykinin release. Neurons isolated from neonatal rat dorsal root ganglia were maintained in primary culture for 1 wk. Cells were then exposed for 30 min at 37 degrees C to graded concentrations of NaCl, mannitol, sucrose, or glycerol (0-600 mOsm) added to isotonic medium, or to isotonic medium at 25 degrees C without or with 462 mOsm mannitol added. Fractional release of substance P (SP) was calculated from supernatant and intracellular SP contents following exposure. Hyperosmolar solutions containing excess NaCl, mannitol, or sucrose all increased fractional SP release equivalently, in an osmolarity-dependent fashion. In marked contrast, hypothermia had no effect on fractional SP release under isotonic or hypertonic conditions. Thus, hyperosmolarity, but not hypothermia, can directly stimulate tachykinin release from cultured rat sensory C-fibers. The lack of effect of glycerol, a solute which quickly crosses cell membranes, suggests that neuronal volume change represents the physical stimulus transduced by C-fibers during hyperosmolar exposure.