Stephen E. Lapinsky

Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada

CONTEXT Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. OBJECTIVE To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. DESIGN, SETTING, AND PATIENTS A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009. MAIN OUTCOME MEASURES The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay. RESULTS Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao(2) to fraction of inspired oxygen [Fio(2)] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29). CONCLUSION Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

Evaluation of A ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome

BACKGROUND A strategy of mechanical ventilation that limits airway pressure and tidal volume while permitting hypercapnia has been recommended for patients with the acute respiratory distress syndrome. The goal is to reduce lung injury due to overdistention. However, the efficacy of this approach has not been established. METHODS Within 24 hours of intubation, patients at high risk for the acute respiratory distress syndrome were randomly assigned to either pressure- and volume-limited ventilation (limited-ventilation group), with the peak inspiratory pressure maintained at 30 cm of water or less and the tidal volume at 8 ml per kilogram of body weight or less, or to conventional ventilation (control group), with the peak inspiratory pressure allowed to rise as high as 50 cm of water and the tidal volume at 10 to 15 ml per kilogram. All other ventilatory variables were similar in the two groups. RESULTS A total of 120 patients with similar clinical features underwent randomization (60 in each group). The patients in the limited-ventilation and control groups were exposed to different mean (+/-SD) tidal volumes (7.2+/-0.8 vs. 10.8+/-1.0 ml per kilogram, respectively; P<0.001) and peak inspiratory pressures (23.6+/-5.8 vs. 34.0+/-11.0 cm of water, P<0.001). Mortality was 50 percent in the limited-ventilation group and 47 percent in the control group (relative risk, 1.07; 95 percent confidence interval, 0.72 to 1.57; P=0.72). In the limited-ventilation group, permissive hypercapnia (arterial carbon dioxide tension, >50 mm Hg) was more common (52 percent vs. 28 percent, P=0.009), more marked (54.4+/-18.8 vs. 45.7+/-9.8 mm Hg, P=0.002), and more prolonged (146+/-265 vs. 25+/-22 hours, P=0.017) than in the control group. The incidence of barotrauma, the highest multiple-organ-dysfunction score, and the number of episodes of organ failure were similar in the two groups; however, the numbers of patients who required paralytic agents (23 vs. 13, P=0.05) and dialysis for renal failure (13 vs. 5, P= 0.04) were greater in the limited-ventilation group than in the control group. CONCLUSIONS In patients at high risk for the acute respiratory distress syndrome, a strategy of mechanical ventilation that limits peak inspiratory pressure and tidal volume does not appear to reduce mortality and may increase morbidity.

Critically Ill Patients With 2009 Influenza A(H1N1) in Mexico

CONTEXT In March 2009, novel 2009 influenza A(H1N1) was first reported in the southwestern United States and Mexico. The population and health care system in Mexico City experienced the first and greatest early burden of critical illness. OBJECTIVE To describe baseline characteristics, treatment, and outcomes of consecutive critically ill patients in Mexico hospitals that treated the majority of such patients with confirmed, probable, or suspected 2009 influenza A(H1N1). DESIGN, SETTING, AND PATIENTS Observational study of 58 critically ill patients with 2009 influenza A(H1N1) at 6 hospitals between March 24 and June 1, 2009. Demographic data, symptoms, comorbid conditions, illness progression, treatments, and clinical outcomes were collected using a piloted case report form. MAIN OUTCOME MEASURES The primary outcome measure was mortality. Secondary outcomes included rate of 2009 influenza (A)H1N1-related critical illness and mechanical ventilation as well as intensive care unit (ICU) and hospital length of stay. RESULTS Critical illness occurred in 58 of 899 patients (6.5%) admitted to the hospital with confirmed, probable, or suspected 2009 influenza (A)H1N1. Patients were young (median, 44.0 [range, 10-83] years); all presented with fever and all but 1 with respiratory symptoms. Few patients had comorbid respiratory disorders, but 21 (36%) were obese. Time from hospital to ICU admission was short (median, 1 day [interquartile range {IQR}, 0-3 days]), and all patients but 2 received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia (median day 1 ratio of Pao(2) to fraction of inspired oxygen, 83 [IQR, 59-145] mm Hg). By 60 days, 24 patients had died (41.4%; 95% confidence interval, 28.9%-55.0%). Patients who died had greater initial severity of illness, worse hypoxemia, higher creatine kinase levels, higher creatinine levels, and ongoing organ dysfunction. After adjusting for a reduced opportunity of patients dying early to receive neuraminidase inhibitors, neuraminidase inhibitor treatment (vs no treatment) was associated with improved survival (odds ratio, 8.5; 95% confidence interval, 1.2-62.8). CONCLUSION Critical illness from 2009 influenza A(H1N1) in Mexico occurred in young individuals, was associated with severe acute respiratory distress syndrome and shock, and had a high case-fatality rate.

Handheld Computing in Medicine

Handheld computers have become a valuable and popular tool in various fields of medicine. A systematic review of articles was undertaken to summarize the current literature regarding the use of handheld devices in medicine. A variety of articles were identified, and relevant information for various medical fields was summarized. The literature search covered general information about handheld devices, the use of these devices to access medical literature, electronic pharmacopoeias, patient tracking, medical education, research, business management, e-prescribing, patient confidentiality, and costs as well as specialty-specific uses for personal digital assistants (PDAs). The authors concluded that only a small number of articles provide evidence-based information about the use of PDAs in medicine. The majority of articles provide descriptive information, which is nevertheless of value. This article aims to increase the awareness among physicians about the potential roles for handheld computers in medicine and to encourage the further evaluation of their use.

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.

Recruitment maneuvers for acute lung injury: A systematic review

RATIONALE There are conflicting data regarding the safety and efficacy of recruitment maneuvers (RMs) in patients with acute lung injury (ALI). OBJECTIVES To summarize the physiologic effects and adverse events in adult patients with ALI receiving RMs. METHODS Systematic review of case series, observational studies, and randomized clinical trials with pooling of study-level data. MEASUREMENTS AND MAIN RESULTS Forty studies (1,185 patients) met inclusion criteria. Oxygenation (31 studies; 636 patients) was significantly increased after an RM (PaO2): 106 versus 193 mm Hg, P = 0.001; and PaO2/FiO2 ratio: 139 versus 251 mm Hg, P < 0.001). There were no persistent, clinically significant changes in hemodynamic parameters after an RM. Ventilatory parameters (32 studies; 548 patients) were not significantly altered by an RM, except for higher PEEP post-RM (11 versus 16 cm H2O; P = 0.02). Hypotension (12%) and desaturation (9%) were the most common adverse events (31 studies; 985 patients). Serious adverse events (e.g., barotrauma [1%] and arrhythmias [1%]) were infrequent. Only 10 (1%) patients had their RMs terminated prematurely due to adverse events. CONCLUSIONS Adult patients with ALI receiving RMs experienced a significant increase in oxygenation, with few serious adverse events. Transient hypotension and desaturation during RMs is common but is self-limited without serious short-term sequelae. Given the uncertain benefit of transient oxygenation improvements in patients with ALI and the lack of information on their influence on clinical outcomes, the routine use of RMs cannot be recommended or discouraged at this time. RMs should be considered for use on an individualized basis in patients with ALI who have life-threatening hypoxemia.

Safety and efficacy of a sustained inflation for alveolar recruitment in adults with respiratory failure.

Objective: To assess the safety and efficacy of a sustained inflation, used as a lung volume recruitment maneuver in ventilated patients with hypoxemic respiratory failure.¶Design: Prospective data collection as part of a quality assurance program following introduction of a lung volume recruitment guideline in the intensive care unit.¶Setting: Academic medical-surgical critical care unit.¶Patients: Hypoxemic patients with bilateral pulmonary infiltrates. Patients with chronic obstructive pulmonary disease, pulmonary barotrauma and hemodynamic instability were excluded.¶Interventions: A sustained inflation using a pressure of 30 to 45 cmH2O was applied for 20 s. The pressure was determined as the lesser of 45 cmH2O or the peak pressure while ventilated at a tidal volume of 12 ml/kg. Intra-arterial blood pressure and pulse oximetry were monitored continuously.¶Measurements and results: Significant improvement in oxygenation occurred in the majority of patients within 10 min. The mean oxygen saturation improved from 86.9 ± 5.5 to 94.3 ± 2.3 % (p < 0.01). No significant adverse effects were noted: hypotension and mild oxygen desaturation occurred in some patients during the 20-s inflation, reversing rapidly after inflation was terminated. No barotrauma occurred.¶Conclusions: A sustained inflation is a safe, clinically applicable method of lung volume recruitment which improves oxygenation in selected patients and may have a role in ventilatory management.

Critical care management of the obstetric patient

PurposeTo review a series of critically ill obstetric patients admitted to a general intensive care unit in a Canadian centre, to assess the spectrum of diseases, interventions required and outcome.MethodsA retrospective chart review was performed of obstetric patients admitted to the intensive care unit of an academic hospital with a high-risk obstetric service, dunng a five-year penod. Data obtained included the admission diagnosis. ICU course and outcome. Daily APACHE II and TISS scores were recorded.ResultsSixty-five obstetric patients, representing 0.26% of deliveries in this hospital, were admitted to the ICU during the study period. All had received prenatal care. Admission diagnoses included obstetric (71%) and nonobstetric (29%) complications. The mean APACHE II score was 6.8 ± 4.2 and mean TISS score was 24 ± 8.1. Twenty-seven patients (42%) required mechanical ventilation. No maternal mortality occurred and the perinatal mortality rate was 11 %.ConclusionsA small proportion of obstetric patients develop complications requiring ICU admission. The out-come in this study was excellent, in contrast to that reported in other published studies with similar ICU admission rates. The universal availability of prenatal care may be an important factor in the outcome of this group of patients. The lack of a specific severity of illness scoring system for the pregnant patient makes comparison of case series difficult.RésuméObjectifsRevoir les dossiers d’une groupe de parturientes sérieusement malades admises à l’unité des soins intensifs (USI) généraux d’un centre hospitalier canadien, évaluer l’éventail des affections, les interventions nécessaires et les résultats obtenus.MéthodesRevue rétrospective de dossiers de parturientes admises à l’USI d’un hôpital universitaire canadien doté d’un service d’obstétrique pour patientes à risques élevés pendant une période de cinq ans. Les données obtenues comprenaient le diagnostic à l’admission, l’évolution à l’USI et les résultats. Les scores APACHE Il et TISS étaient enregistrés quotidiennement.RésultatsSoixante-cinq parturientes représentant 0,26% des accouchements de l’hôpital ont été admises à l’USI pendant la période étudiée. Toutes avaient bénéficié des soins prénataux. Les patientes étaient admises pour des complications obstétncales (71%) ou autres (29%). Les scores APACHE et TilSS moyens étaient respectivement 6.8 ± 4.2 et 24 ± 8.1. Vingt–sept patientes (42%) ont été ventilées mécaniquement. Il n’y a pas eu de mortalité maternelle et le taux de mortalité périnatale était de 11 %.ConclusionsUne faible proportion des partunentes développent des complications nécessitant des soins intensifs. Pour cette étude, les résultats sont excellents, contrairement à d’autres publiés ailleurs comportant des taux d’admission aux soins intensifs identiques. L’universalité de l’accès aux soins prénataux pourrait influencer considérablement les résultats dans ce groupe de patientes. L’absence d’un système de score spécifique à la gravité des affections de la grossesse rend la comparaison entre séries difficile.

Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury.

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.

H1N1 novel influenza A in pregnant and immunocompromised patients

Objective:To describe the increased risk of severe disease and the appropriate management of patients at high risk such as pregnant women and immunosuppressed patients who acquire novel influenza A (H1N1). Design:Review of the literature regarding influenza A in these patient groups, and review of published and unpublished data with regard to novel influenza A (H1N1). Main Results:Pregnant women are at increased risk for severe pneumonitis and respiratory failure from influenza infection, particularly during pandemics, including the current pandemic. Fetal morbidity is significant, usually resulting from maternal fever and severe hypoxemia. Early antiviral therapy using oseltamivir may be beneficial, and intensive care unit support should target adequate oxygenation at all times. Immunosuppressed patients are at increased risk for influenza, as well as at risk for more severe or prolonged infection. Patients after hematopoietic stem cell transplantation, after lung transplantation, and those receiving chemotherapy for leukemia are at highest risk, whereas the risk for human immunodeficiency virus-infected individuals appears relatively low. Treatment with antiviral therapy may be beneficial, even after the usual cut-off of 48 hrs after symptom onset. Conclusions:Optimal management of these patients is preventive by influenza vaccination, but the neuraminidase inhibitor antiviral agents provide effective treatment.