David Hallett

Has mortality from acute respiratory distress syndrome decreased over time?: A systematic review.

RATIONALE It is commonly stated that mortality from acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) is decreasing. OBJECTIVES To systematically review the literature assessing ARDS mortality over time and to determine patient- and study-level factors independently associated with mortality. METHODS We searched multiple databases (MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL) for prospective observational studies or randomized controlled trials (RCTs) published during the period 1984 to 2006 that enrolled 50 or more patients with ALI/ARDS and reported mortality. We pooled mortality estimates using random-effects meta-analysis and examined mortality trends before and after 1994 (when a consensus definition of ALI/ARDS was published) and factors associated with mortality using meta-regression models. MEASUREMENTS AND MAIN RESULTS Of 4,966 studies, 89 met inclusion criteria (53 observational, 36 RCTs). There was a total of 18,900 patients (mean age 51.6 years; 39% female). Overall pooled weighted mortality was 44.3% (95% confidence interval [CI], 41.8-46.9). Mortality decreased with time in observational studies conducted before 1994; no temporal associations with mortality were demonstrated in RCTs (any time) or observational studies (after 1994). Pooled mortality from 1994 to 2006 was 44.0% (95% CI, 40.1-47.5) for observational studies, and 36.2% (95% CI, 32.1-40.5) for RCTs. Meta-regression identified study type (observational versus RCT, odds ratio, 1.36; 95% CI, 1.08-1.73) and patient age (odds ratio per additional 10 yr, 1.27; 95% CI, 1.07-1.50) as the only factors associated with mortality. CONCLUSIONS A decrease in ARDS mortality was only seen in observational studies from 1984 to 1993. Mortality did not decrease between 1994 (when a consensus definition was published) and 2006, and is lower in RCTs than observational studies.

Prospective trial of high-frequency oscillation in adults with acute respiratory distress syndrome

ObjectiveTo evaluate the safety and efficacy of high-frequency oscillatory ventilation (HFOV) in adult patients with the acute respiratory distress syndrome (ARDS) and oxygenation failure. DesignProspective, clinical study. SettingIntensive care and burn units of two university teaching hospitals. PatientsTwenty-four adults (10 females, 14 males, aged 48.5 ± 15.2 yrs, Acute Physiology and Chronic Health Evaluation II score 21.5 ± 6.9) with ARDS (lung injury score 3.4 ± 0.6, Pao2/Fio2 98.8 ± 39.0 mm Hg, and oxygenation index 32.5 ± 19.6) who met one of the following criteria: Pao2 ≤65 mm Hg with Fio2 ≥0.6, or plateau pressure ≥35 cm H2O. InterventionsHFOV was initiated in patients with ARDS after varying periods of conventional ventilation (CV). Mean airway pressure (Paw) was initially set 5 cm H2O greater than Paw during CV, and was subsequently titrated to maintain oxygen saturation between 88% and 93% and Fio2 ≤0.60. Measurements and Main ResultsFio2, Paw, pressure amplitude of oscillation, frequency, blood pressure, heart rate, and arterial blood gases were monitored during the transition from CV to HFOV, and every 8 hrs thereafter for 72 hrs. In 16 patients who had pulmonary artery catheters in place, cardiac hemodynamics were recorded at the same time intervals. Throughout the HFOV trial, Paw was significantly higher than that applied during CV. Within 8 hrs of HFOV application, and for the duration of the trial, Fio2 and Paco2 were lower, and Pao2/Fio2 was higher than baseline values during CV. Significant changes in hemodynamic variables following HFOV initiation included an increase in pulmonary artery occlusion pressure (at 8 and 40 hrs) and central venous pressure (at 16 and 40 hrs), and a reduction in cardiac output throughout the course of the study. There were no significant changes in systemic or pulmonary pressure associated with initiation and maintenance of HFOV. Complications occurring during HFOV included pneumothorax in two patients and desiccation of secretions in one patient. Survival at 30 days was 33%, with survivors having been mechanically ventilated for fewer days before institution of HFOV compared with nonsurvivors (1.6 ± 1.2 vs. 7.8 ± 5.8 days;p = .001). ConclusionsThese findings suggest that HFOV has beneficial effects on oxygenation and ventilation, and may be a safe and effective rescue therapy for patients with severe oxygenation failure. In addition, early institution of HFOV may be advantageous.

Canadian survey of the use of sedatives, analgesics, and neuromuscular blocking agents in critically ill patients.

Objectives:To characterize the perceived utilization of sedative, analgesic, and neuromuscular blocking agents, the use of sedation scales, algorithms, and daily sedative interruption in mechanically ventilated adults, and to define clinical factors that influence these practices. Design:Cross-sectional mail survey. Participants:Canadian critical care practitioners. Measurements and Main Results:A total of 273 of 448 eligible physicians (60%) responded. Respondents were well distributed with regard to age, years of practice, specialist certification, size of intensive care unit and hospital, and location of practice. Twenty-nine percent responded that a protocol/care pathway/guideline for the use of sedatives or analgesics is currently in use in their intensive care unit. Daily interruption of continuous infusions of sedatives or analgesics is practiced by 40% of intensivists. A sedation scoring system is used by 49% of respondents. Of these, 67% use the Ramsay scale, 10% use the Sedation-Agitation Scale, 9% use the Glasgow Coma Scale, and 8% use the Motor Activity Assessment Scale. Only 3.7% of intensivists use a delirium scoring system in their intensive care units. Only 22% of respondents currently have a protocol for the use of neuromuscular blocking agents in their intensive care unit, and 84% of respondents use peripheral nerve stimulation for monitoring. In patients receiving neuromuscular blocking agents for >24 hrs, 63.7% of respondents discontinue the neuromuscular blocking agent daily. Intensivists working in university-affiliated hospitals are more likely to employ a sedation protocol and scale (p < .0001), as are intensivists working in larger intensive care units (≥15 beds, p < .01). Intensivists with anesthesiology training (and no formal critical care training) are more likely to use a protocol and sedation scale, and critical care–trained intensivists are more likely to use daily interruption. Younger physicians (<40 yrs) are more likely to practice daily interruption (p = .0092). Conclusions:There is significant variation in critical care sedation, analgesia, and neuromuscular blockade practice. Given the potential effect of practices regarding these medications on patient outcome, future research and educational efforts related to evidence-based protocols for the use of these agents in mechanically ventilated patients might be worthwhile.

Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis

BackgroundInfluenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains.MethodsWe identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%).ResultsWe included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%).ConclusionsThe TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.

A randomized trial of daily awakening in critically ill patients managed with a sedation protocol: a pilot trial.

Objective:Protocolized sedation (PS) and daily sedative interruption (DI) in critically ill patients have both been shown to shorten the durations of mechanical ventilation (MV) and intensive care unit (ICU) stay. Our objective was to determine the safety and feasibility of a randomized trial to determine whether adults managed with both PS + DI have a shorter duration of MV than patients managed with PS alone. Design:Prospective randomized, concealed, unblinded, multicenter, pilot trial. Setting:Three university-affiliated medical-surgical ICUs. Patients:Sixty-five adults anticipated to require MV >48 hrs and receiving sedative/analgesic infusions. Interventions:Patients were randomized to PS alone, or PS + DI. PS was implemented by bedside nurses; sedatives/analgesics were titrated to achieve Sedation Agitation Score (SAS) 3–4. The PS + DI group also had infusions interrupted daily until the patients awoke. Measurements and Main Results:Diagnosis, age [mean ± sd] (53 ± 18.3 vs. 62.1 ± 16.7 yrs) and Acute Physiology and Chronic Health Evaluation II (27.7 ± 8.4 vs. 26.6 ± 8.4) were similar in the PS and PS + DI groups, respectively. The median duration of MV in the PS and PS + DI groups was 8.0 vs. 10.5 days, and ICU stay was 10.0 vs. 13.0 days, respectively. The SAS was within target range (3–4) in 59% of 9,611 measurements, and within an acceptable range (2–5) in 86% of measurements. Self-assessed nursing and respiratory therapist workload was low in the majority of the cohort. Adverse events were similar in both groups. Patient recruitment was slower than projected (1.5 patients/mo). Conclusion:This pilot trial comparing PS vs. PS + DI confirmed the safety and acceptability of the sedation protocol and DI, and guided important modifications to the protocol, thus enhancing the feasibility of a future multicenter trial. This trial was not designed to detect small but significant differences in clinically important outcomes.

Acute oxygenation response to inhaled nitric oxide when combined with high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome.

ObjectiveTo prospectively evaluate the oxygenation effect of inhaled nitric oxide (INO) delivered during high-frequency oscillatory ventilation in adult patients with the acute respiratory distress syndrome and oxygenation failure. DesignProspective, clinical study. SettingIntensive care unit of a university teaching hospital. PatientsA total of 23 adults (14 women, 9 men, 44.9 ± 17.5 yrs, Acute Physiology and Chronic Health Evaluation II score of 28.6 ± 7.1) with acute respiratory distress syndrome (lung injury score, 3.5 ± 0.4) with Fio2 of ≥0.6 and mean airway pressure of ≥28 cm H2O. InterventionsINO was initiated at a dose of 5 ppm, and subsequently titrated according to a protocol, to determine the dose (5, 10, or 20 ppm) resulting in the greatest increase in Pao2/Fio2. Blood gas measurements were obtained 10–15 mins after initiation or any increase in INO dosage to assess the effect on Pao2/Fio2. Measurements and Main ResultsArterial blood gases and ventilator settings were recorded at four time points: during conventional ventilation just before initiating high-frequency oscillatory ventilation, during high-frequency oscillatory ventilation just before initiating INO, after 30 mins on the optimal dose of INO, and 8–12 hrs after starting INO. Oxygenation index ([Fio2 × mean airway pressure × 100]/Pao2) and Pao2/Fio2 ratios were calculated at the same time intervals. At 30 mins after INO initiation, 83% of patients had a significant increase in blood oxygen tension, defined as ≥20% increase in Pao2/Fio2. The mean change in Pao2/Fio2 at 30 mins was 38%. In these 19 patients, Pao2/Fio2 was highest at 20 ppm in four patients, at 10 ppm in eight patients, and at 5 ppm in seven patients. Compared with baseline measurements, Pao2/Fio2 improved significantly at both 30 mins (112 ± 59 vs. 75 ± 32, p = .01) and 8–12 hrs after INO initiation (146 ± 52 vs. 75 ± 32, p < .0001). In addition, oxygenation index was reduced at 8–12 hrs compared with baseline measurements (26 ± 13 vs. 40 ± 17, p = .08). ConclusionsINO delivered at doses of 5 to 20 ppm during high-frequency oscillatory ventilation increases Pao2/Fio2 and may be a safe and effective rescue therapy for patients with severe oxygenation failure.

Morbidity and Mortality of Patients With Invasive Group A Streptococcal Infections Admitted to the ICU

STUDY OBJECTIVES To describe the clinical features and outcome of patients with invasive group A streptococcal (GAS) infections admitted to the ICU. DESIGN Prospective, population-based surveillance for invasive GAS infections was conducted in Ontario from January 1992 until June 2002. All 62 patients meeting clinical and/or histopathologic criteria for invasive GAS who were admitted to the ICUs of four university-affiliated hospitals in Toronto, Canada were included. Demographic and clinical information were obtained retrospectively by chart review. ICU morbidity data included the occurrence of organ dysfunction (renal, hepatic, coagulation, ARDS), treatment, and interventions such as hemodialysis and mechanical ventilation. MEASUREMENTS AND RESULTS ARDS developed in 34%, renal dysfunction developed in 55%, hepatic dysfunction developed in 64%, and coagulopathy developed in 69% of patients. A total of 56% of patients were treated with IV polyspecific IgG (IVIG), 81% were intubated and placed on mechanical ventilation, and 21% required renal replacement therapy. The median durations of ICU and hospital stay were 5.3 days and 15.0 days, respectively. The overall mortality was 40%. Mortality correlated directly with acute physiology and chronic health evaluation II score and the number of dysfunctional organs. Survivors were younger, had lower severity of illness scores, fewer dysfunctional organs, and were less likely to have shock or to receive treatment with vasopressors, mechanical ventilation, or pulmonary artery catheters. There was no association between the use of IVIG, surgical intervention, or clindamycin, and survival. Variables independently associated with mortality on multivariable analysis were the presence of coagulopathy (p = 0.0005) and liver dysfunction (p = 0.0123). CONCLUSIONS Patients with invasive GAS infection admitted to the ICU have a high mortality rate. In this group of patients, coagulopathy and liver failure were independently associated with mortality. We did not observe any association between the use of IVIG, surgical intervention, or clindamycin, and survival.

Survey of information technology in Intensive Care Units in Ontario, Canada

BackgroundThe Intensive Care Unit (ICU) is a data-rich environment where information technology (IT) may enhance patient care. We surveyed ICUs in the province of Ontario, Canada, to determine the availability, implementation and variability of information systems.MethodsA self-administered internet-based survey was completed by ICU directors between May and October 2006. We measured the spectrum of ICU clinical data accessible electronically, the availability of decision support tools, the availability of electronic imaging systems for radiology, the use of electronic order entry and medication administration systems, and the availability of hardware and wireless or mobile systems. We used Fishers Exact tests to compare IT availability and Classification and Regression Trees (CART) to estimate the optimal cut-point for the number of computers per ICU bed.ResultsWe obtained responses from 50 hospitals (68.5% of institutions with level 3 ICUs), of which 21 (42%) were university-affiliated. The majority electronically accessed laboratory data and imaging reports (92%) and used picture archiving and communication systems (PACS) (76%). Other computing functions were less prevalent (medication administration records 46%, physician or nursing notes 26%; medication order entry 22%). No association was noted between IT availability and ICU size or university affiliation. Sites used clinical information systems from15 different vendors and 8 different PACS systems were in use. Half of the respondents described the number of computers available as insufficient. Wireless networks and mobile computing systems were used in 23 ICUs (46%).ConclusionOntario ICUs demontrate a high prevalence of the use of basic information technology systems. However, implementation of the more complex and potentially more beneficial applications is low. The wide variation in vendors utilized may impair information exchange, interoperability and uniform data collection.

Temporal change, reproducibility, and interobserver variability in pressure-volume curves in adults with acute lung injury and acute respiratory distress syndrome.

ObjectivesTo assess the reproducibility of the static pressure-volume curve of the respiratory system by using a “mini-syringe” technique; to assess the temporal change in upper (UIP) and lower inflection points (LIP) measured from pressure-volume curves of the respiratory system; to assess the inter- and intraobserver variability in detection of the UIP and LIP in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); and to compare the syringe and multiple occlusion techniques for determining LIP and UIP. DesignProspective observational study. SettingAcademic medical-surgical critical care unit. PatientsConsecutive patients with ALI or ARDS. InterventionsStatic inspiratory pressure-volume curves of the respiratory system were determined twice on day 1 of diagnosis of ALI/ARDS and then once daily for up to 6 days by using the syringe technique. Pressure-volume curves were determined from zero positive end-expiratory pressure. At each time point, three separate measurements of the pressure-volume curve were made to determine reproducibility. A 100-mL graduated syringe was used to inflate patients’ lungs with 50- to 100-mL increments up to an airway pressure of 45 cm H2O or a total volume of 2 L; each volume step was maintained for 2–3 secs until a plateau airway pressure was recorded. On day 1, the static pressure-volume curve also was determined by using the multiple occlusion technique. In a random and blinded sequence, the pressure-volume curves were examined visually by three critical care physicians on three different occasions, to determine the intra- and interobserver variability in visual detection of the LIP and UIP. Observers were given objective instructions to visually identify LIP and UIP. Measurements and Main ResultsEleven patients were enrolled, with a total of 134 pressure-volume curves generated. LIP and UIP could be detected in 90–94% and 61–68% of curves, respectively. When the three successive pressure-volume curves were compared, both the LIP and UIP were within 3 cm H2O in >65% of curves. The index of reliability (intraclass correlation coefficient) in LIP and UIP was 0.92 and 0.89 for interobserver variability and 0.90 and 0.88 for intraobserver variability. Daily variability was as high as 7 cm H2O for LIP and 5 cm H2O for UIP. When pressure-volume curves obtained by using the multiple occlusion and syringe techniques were compared, LIP was within 2 cm H2O, and UIP was within 4 cm H2O with the two techniques. ConclusionsThe static pressure-volume curve of the respiratory system is reasonably reproducible, thus avoiding the need for multiple measurements at a single time. We found excellent interobserver and intraobserver correlation in manual identification of the LIP and UIP. Both LIP and UIP show appreciable daily variability in patients with ALI/ARDS. The multiple occlusion and syringe techniques generate similar values for LIP and UIP.

Predictors of mortality in patients undergoing autologous hematopoietic cell transplantation admitted to the intensive care unit

Between January 2001 and July 2006, 1013 patients received autologous hematopoietic cell transplants (AHCT) at Canadas largest transplant center. In this retrospective cohort study of AHCT patients admitted to the intensive care unit (ICU), we describe the outcomes following ICU admission and the variables measured in the first 24 h of ICU admission associated with overall ICU mortality. Results indicate a 3.3% ICU admission rate (n=34) with 13 deaths (1% overall mortality rate, 38% in ICU mortality rate). The worst outcome was in AL amyloid patients of whom 28% were admitted to the ICU, with an ICU mortality rate of 55%. The Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) score in the first 24 h were statistically associated with mortality by univariate analysis. Other variables measured at 24 h and associated with ICU mortality included multiorgan failure, mechanical ventilation, inotropic support >4 h and Gram-negative sepsis. Our data indicate that ICU admission in the autotransplant population is rare and that it is influenced by underlying diagnosis, with AL amyloid patients having the highest risk. Our observations may assist clinical decision-making regarding the continuation of intensive care delivered 24 h after ICU admission.